[go: up one dir, main page]

US20230293480A1 - Cannabis based therapeutic and method of use - Google Patents

Cannabis based therapeutic and method of use Download PDF

Info

Publication number
US20230293480A1
US20230293480A1 US18/131,052 US202318131052A US2023293480A1 US 20230293480 A1 US20230293480 A1 US 20230293480A1 US 202318131052 A US202318131052 A US 202318131052A US 2023293480 A1 US2023293480 A1 US 2023293480A1
Authority
US
United States
Prior art keywords
c15h24o
c15h26o
diene
c15h22o
c10h16o
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
US18/131,052
Other versions
US12303488B2 (en
Inventor
Nicola Michael SPIRTOS
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Yuzu Lv LLC
Original Assignee
Yuzu Lv LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Yuzu Lv LLC filed Critical Yuzu Lv LLC
Priority to US18/131,052 priority Critical patent/US12303488B2/en
Assigned to YUZU LV LLC reassignment YUZU LV LLC ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: Spirtos, Nicola Michael
Assigned to YUZU LV LLC reassignment YUZU LV LLC CHANGE OF ADDRESS Assignors: YUZU LV LLC
Priority to US18/220,856 priority patent/US12458653B2/en
Publication of US20230293480A1 publication Critical patent/US20230293480A1/en
Application granted granted Critical
Publication of US12303488B2 publication Critical patent/US12303488B2/en
Active legal-status Critical Current
Adjusted expiration legal-status Critical

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/658Medicinal preparations containing organic active ingredients o-phenolic cannabinoids, e.g. cannabidiol, cannabigerolic acid, cannabichromene or tetrahydrocannabinol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/01Hydrocarbons
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/01Hydrocarbons
    • A61K31/015Hydrocarbons carbocyclic
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/045Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/045Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05Phenols
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12Carboxylic acids; Salts or anhydrides thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/46Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/08Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/04Centrally acting analgesics, e.g. opioids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/30Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/36Opioid-abuse

Definitions

  • compositions comprising: tetrahydrocannabinol (THC) and cannabidiol (CBD) in a THC:CBD ratio of from 1:1.5 to 3:1 by weight; and one or more terpenes.
  • THC:CBD ratio is from 1.5:1 to 2:1. In some embodiments, the THC:CBD ratio is about 1.5:1.
  • the pharmaceutical composition comprises about 15-20 mg tetrahydrocannabinol (THC) per dose. In some embodiments, the pharmaceutical composition comprises 10-12 mg cannabidiol (CBD).
  • THC tetrahydrocannabinol
  • CBD cannabidiol
  • the one or more terpenes comprise ⁇ -myrcene, ⁇ -caryophyllene, ocimene, ⁇ -pinene, ⁇ -humulene, linalool, p-cymene, camphene, cis-nerolidol, terpinolene, isopulegol, caryophyllene oxide, ⁇ -limonene, geraniol, guaiol, ⁇ -bisabolol, 3-carene, ⁇ -pinene, ⁇ -terpinene, or a combination thereof.
  • rein the one or more terpenes comprise ⁇ -myrcene, ⁇ -caryophyllene, ocimene, ⁇ -pinene, and ⁇ -humulene.
  • the one or more terpenes comprise ⁇ -myrcene, and wherein the pharmaceutical composition comprises 30-60 mg of ⁇ -myrcene per dose.
  • the one or more terpenes comprise ⁇ -caryophyllene, and wherein the pharmaceutical composition comprises 2.5-5 mg of ⁇ -caryophyllene per dose.
  • the one or more terpenes comprise ocimene, and wherein the pharmaceutical composition comprises 2.3-4.7 mg of ocimene per dose.
  • the one or more terpenes comprise ⁇ -pinene, and wherein the pharmaceutical composition comprises 1.1-2.1 mg of ⁇ -pinene per dose.
  • the one or more terpenes comprise ⁇ -humulene, and wherein the pharmaceutical composition comprises 0.8-1.6 mg of ⁇ -humulene per dose.
  • the one or more terpenes comprise ⁇ -myrcene, ⁇ -caryophyllene, ocimene, ⁇ -pinene, and ⁇ -humulene; and wherein the pharmaceutical composition comprises about 30-60 mg of the ⁇ -mycene, about 2.5-5 mg of the ⁇ -caryophyllene, about 2.3-4.7 mg of the ocimene, about 1.1-2.1 mg of the ⁇ -pinene, and about 0.8-1.6 mg of the ⁇ -humulene per dose.
  • the pharmaceutical composition is formulated as a liquid, a pill, a gel capsule, a vaporizable liquid, a vaporizable solid, a transdermal ointment or salve, or a transdermal patch.
  • the pharmaceutical composition is formulated as a liquid.
  • the liquid comprises citric acid, blue agave, glycerine, one or more lorann oils, food coloring, or a combination thereof.
  • the liquid comprises: about 1% to 7% w/w citric acid; about 40% to 49% w/w blue agave; about 40% to 49% w/w glycerin; about 0.1% to 1.5% w/w lorann oils; about 0.01 to 0.4% food coloring; or a combination thereof.
  • the liquid comprises: about 3-5% w/w citric acid; about 45-49% w/w blue agave; about 45-49% w/w glycerin; about 0.7-0.9% w/w lorann oils; and about 0.1-0.3% food coloring.
  • the pharmaceutical composition is for use in the treatment of opioid addiction.
  • the pharmaceutical composition is for use in the treatment of pain.
  • the pharmaceutical composition is for use in the treatment of chemotherapy-induced nausea and vomiting.
  • the pharmaceutical composition can be any pharmaceutical composition disclosed herein.
  • the pharmaceutical composition is administered every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours.
  • the pharmaceutical composition is administered every 6, 8 or 12 hours.
  • the subjects opioid use decreases by at least 50% within 5 weeks of beginning treatment as determined by morphine equivalency of opioids used.
  • FIG. 1 a &b illustrates weekly pill counts in chart form ( FIG. 1 a ) and graph form with regression analysis ( FIG. 1 b ).
  • FIG. 2 a &b illustrates weekly pill counts in morphine equivalents in tabular form ( FIG. 2 a ) and graph form with regression analysis ( FIG. 2 b ).
  • the present disclosure relates to therapeutics, and more especially the use of cannabinoid-based therapeutics, for use in treating those known to have chronic pain. In some cases, the chronic pain may have been treated using opiates.
  • the present disclosure also relates to cannabinoid-based therapeutics for use in treating opioid addiction.
  • Each dose of syrup contained either 10 mg/ml of both delta-9-tetracannabinol (THC) and cannabidiol (CBD) or 20 mg of THC and 10 mg of CBD.
  • THC delta-9-tetracannabinol
  • CBD cannabidiol
  • Cannabis contains at least 63 cannabinoids but two are best understood studied.
  • the first, delta-9 tetrahydrocannabinol (THC) is responsible for the psychoactive effects that is widely associated with cannabis .
  • the other main active component, cannabidiol (CBD) has no psychoactive effect associated with its consumption but is thought to provide anti-neoplastic, analgesic and antineuroleptic effects per the literature.
  • CBD cannabidiol
  • CBD binds as an antagonist to the cannabinoid receptor CB1 but the bond between THC and the same receptor is at least 100 times stronger. CBD also antagonizes the action on the cannabinoid G protein-coupled receptor GPR55, which is thought to be responsible the different neuromodulatory actions as the CB1 receptor. Claims of the subjective effects associated with cannabis ingestion include improvement in mood; relaxation; and increased sensitivity. On the other hand THC ingestion has been associated with less than desirable adverse effects such as agitation; panic disorder; depression and even psychosis.
  • Cannabinoids have an effect on serotonergic systems, including increasing cerebral production of 5-hydroxytryptamine (5-HT), serotonin while decreasing its uptake at the synapse level.
  • THC has been found to have dopaminergic antagonistic actions which may contribute to its beneficial profile regarding pain control.
  • phytocannabinoids such as cannabichromene (CBC), cannabigerol (CBG) as well as a number of terpenoids likely contribute its analgesic effect.
  • CBC and CBG have significant anti-inflamatory and analgesic effects over and beyond that associated with THC.
  • B-caryophyllene has been shown to be a selective CB2 agonist and other terpenes such as linalool and a-Pinene have analgesic and anti-inflamatory effects respectively.
  • Myrcene other the other hand has been shown to have analgesic effects mediated through an opioid-like action.
  • cannabis Used in combination with opioid pain medications, cannabis can lower opioid side effects, cravings, and withdrawal severity, as well as enhance the analgesic effects of opioids, thereby allowing for lower doses and less risk of overdose.
  • An embodiment of the present disclosure is the therapeutic compound for the use in treating chronic pain and like disorders and preferably in liquid form compromising a formulation including cannabinoids, but not limited to delta-9—tetrahydrocannabinol and cannabidiol.
  • the compound may optionally include any terpene or terpinoid present in a cannabis plant.
  • a subject suffering from chronic pain is orally administered a therapeutically effective amount of the compound so as to alleviate, cure or prevent the symptoms associated with chronic pain.
  • Another embodiment of the present disclosure is the therapeutic compound for the use in treating chronic pain and like disorders and preferably in a pill form compromising a formulation including cannabinoids, but not limited to delta-9-tetrahydrocannabinol and cannabidiol.
  • the compound may optionally include any terpene or terpinoid present in a cannabis plant.
  • a subject suffering from chronic pain is orally administered a therapeutically effective amount of the compound so as to alleviate, cure or prevent the symptoms associated with chronic pain
  • Another embodiment of the present disclosure is the therapeutic compound for the use in treating chronic pain and like disorders and preferably in suppository form compromising a formulation including cannabinoids, but not limited to delta-9-tetrahydrocannabinol and cannabidiol.
  • the compound may optionally include any terpene or terpinoid present in a cannabis plant.
  • a subject suffering from chronic pain is orally administered a therapeutically effective amount of the compound so as to alleviate, cure or prevent the symptoms associated with chronic pain
  • Another embodiment of the present disclosure is the therapeutic compound for the use in treating chronic pain and like disorders and preferably in capsule form compromising a formulation including cannabinoids, but not limited to delta-9-tetrahydrocannabinol and cannabidiol.
  • the compound may optionally include any terpene or terpinoid present in a cannabis plant.
  • a subject suffering from chronic pain is orally administered a therapeutically effective amount of the compound so as to alleviate, cure or prevent the symptoms associated with chronic pain.
  • Another embodiment of the present disclosure is the therapeutic compound for the use in treating chronic pain and like disorders and preferably in a transdermal form compromising a formulation including cannabinoids, but not limited to delta-9-tetrahydrocannabinol and cannabidiol.
  • the compound may optionally include any terpene or terpinoid present in a cannabis plant.
  • a subject suffering from chronic pain is transdermally administered a therapeutically effective amount of the compound so as to alleviate, cure or prevent the symptoms associated with chronic pain.
  • Another embodiment of the present disclosure is the therapeutic compound for the use in treating chronic pain and like disorders and preferably in an inhalable/nebulized form compromising a formulation including cannabinoids, but not limited to delta-9-tetrahydrocannabinol and cannabidiol.
  • the compound may optionally include any terpene or terpinoid present in a cannabis plant.
  • a subject suffering from chronic pain is inhaled in a therapeutically effective amount of the compound so as to alleviate, cure or prevent the symptoms associated with chronic pain
  • the cannabinoid disclosed herein may include any of the identified cannabinoids, but not limited to THC (Tetrahydrocannabinol); THCA (Tetrahydrocannabinolic acid); CBD (Cannabidiol); CBDA (Cannabidiolic Acid); CBN (Cannabinol); CBG (Cannabigerol); CBC (Cannabichromene); CBL (Cannabicyclol); CBV (Cannabivarin); THCV (Tetrahydrocannabivarin); CBDV (Cannabidivarin); CBCV (Cannabichromevarin); CBGV (Cannabigerovarin); CBGM (Cannabigerol Monomethyl Ether); CBE (Cannabielsoin); CBT (Cannabicitran); (OTHC) 10-Oxo-delta-6a-tetrahydrocannabinol; (CBCF) Cannabichromanon; (CBF) Cannabifuran; Cann
  • terpene disclosed herein may, but is not limited to, any single or combination of the terpenes listed in table 1.
  • An exemplary therapeutic compound conforming with any of the disclosed embodiments may comprise for instance a compound including at least two of delta-9-tetrahydrocannabinol or tetrahydrocannabinolic acid, and cannabidiol and optionally at least one of the listed terpenes Still further an exemplary therapeutic compound conforming with any of the disclosed embodiments may comprise for instance a compound including 20 mg of delta-9-tetrahydrocannabinol and 10 mg of cannabidiol preferably administered every ⁇ -8 hours as needed.
  • Embodiment 1 A pharmaceutical composition comprising: (a) tetrahydrocannabinol (THC) and cannabidiol (CBD) in a THC:CBD ratio of from 1:1.5 to 3:1 by weight; and (b) one or more terpenes listed in Table 1.
  • THC tetrahydrocannabinol
  • CBD cannabidiol
  • Embodiment 2 The pharmaceutical composition of embodiment 1, wherein the THC:CBD ratio is about: 1:1.5, 1:1.4, 1:1.3, 1:1.2, 1:1.1, 1:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, 2:1, 2.1:1, 2.2:1, 2.3:1, 2.4:1, 2.5:1, 2.6:1, 2.7:1, 2.8:1, 2.9:1, or 3:1.
  • Embodiment 3 The pharmaceutical composition of embodiment 1, wherein the THC:CBD ratio is from 1.5:1 to 2:1.
  • Embodiment 4 The pharmaceutical composition of embodiment 1, wherein the THC:CBD ratio is about 1.5:1.
  • Embodiment 5 The pharmaceutical composition of any one of embodiments 1-4, wherein the pharmaceutical composition comprises: 1-50 mg, 5-40 mg, 7.5-30 mg, 10-20 mg, or 12.5-17.5 mg tetrahydrocannabinol (THC) per dose.
  • THC tetrahydrocannabinol
  • Embodiment 6 The pharmaceutical composition of any one of embodiments 1-4, wherein the pharmaceutical composition comprises about: 1 mg, 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg, 17.5 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, or 50 mg tetrahydrocannabinol (THC) per dose.
  • THC tetrahydrocannabinol
  • Embodiment 7 The pharmaceutical composition of any one of embodiments 1-4, wherein the pharmaceutical composition comprises about 10-20 mg tetrahydrocannabinol (THC) per dose.
  • THC tetrahydrocannabinol
  • Embodiment 8 The pharmaceutical composition of any one of embodiments 1-4, wherein the pharmaceutical composition comprises about 15-20 mg tetrahydrocannabinol (THC) per dose.
  • THC tetrahydrocannabinol
  • Embodiment 9 The pharmaceutical composition of any one of embodiments 1-8, wherein the pharmaceutical composition comprises: 1-35 mg, 2.5-30 mg, 5-25 mg, ⁇ -14 mg, 10-12 mg cannabidiol (CBD) per dose.
  • CBD cannabidiol
  • Embodiment 10 The pharmaceutical composition of any one of embodiments 1-8, wherein the pharmaceutical composition comprises about: 1 mg, 1.5 mg, 2 mg, 2.5 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, 17.5 mg, 20 mg, 22.5 mg, 25 mg, 27.5 mg, or 30 mg cannabidiol (CBD) per dose.
  • CBD cannabidiol
  • Embodiment 11 The pharmaceutical composition of any one of embodiments 1-8, wherein the pharmaceutical composition comprises ⁇ -14 mg cannabidiol (CBD).
  • CBD cannabidiol
  • Embodiment 12 The pharmaceutical composition of any one of embodiments 1-8, wherein the pharmaceutical composition comprises 10-12 mg cannabidiol (CBD).
  • CBD cannabidiol
  • Embodiment 13 The pharmaceutical composition of any one of embodiments 1-12, wherein the one or more terpenes comprise ⁇ -myrcene, ⁇ -caryophyllene, ocimene, ⁇ -pinene, ⁇ -humulene, linalool, p-cymene, camphene, cis-nerolidol, terpinolene, isopulegol, caryophyllene oxide, ⁇ -limonene, geraniol, guaiol, ⁇ -bisabolol, 3-carene, ⁇ -pinene, ⁇ -terpinene, or a combination thereof.
  • the one or more terpenes comprise ⁇ -myrcene, ⁇ -caryophyllene, ocimene, ⁇ -pinene, ⁇ -humulene, linalool, p-cymene, camphene, cis-nerolidol
  • Embodiment 14 The pharmaceutical composition of any one of embodiments 1-12, wherein the one or more terpenes comprise ⁇ -myrcene, ⁇ -caryophyllene, ocimene, ⁇ -pinene, ⁇ -humulene, linalool, p-cymene, and camphene.
  • the one or more terpenes comprise ⁇ -myrcene, ⁇ -caryophyllene, ocimene, ⁇ -pinene, ⁇ -humulene, linalool, p-cymene, and camphene.
  • Embodiment 15 The pharmaceutical composition of any one of embodiments 1-12, wherein the one or more terpenes comprise ⁇ -myrcene, ⁇ -caryophyllene, ocimene, ⁇ -pinene, and ⁇ -humulene.
  • Embodiment 16 The pharmaceutical composition of any one of embodiments 1-12, wherein the one or more terpenes comprise ⁇ -myrcene, ocimene, cis-nerolidol, terpinolene, isopulegol, caryophyllene oxide, ⁇ -limonene, geraniol, guaiol, and ⁇ -bisabolol.
  • Embodiment 17 The pharmaceutical composition of any one of embodiments 1-12, wherein the one or more terpenes comprise ⁇ -myrcene, ocimene, cis-nerolidol, terpinolene, isopulegol, caryophyllene oxide, ⁇ -limonene, geraniol, guaiol, ⁇ -bisabolol, and 3-carene.
  • the one or more terpenes comprise ⁇ -myrcene, ocimene, cis-nerolidol, terpinolene, isopulegol, caryophyllene oxide, ⁇ -limonene, geraniol, guaiol, ⁇ -bisabolol, and 3-carene.
  • Embodiment 18 The pharmaceutical composition of any one of embodiments 1-12, wherein the one or more terpenes comprise ⁇ -myrcene, ⁇ -caryophyllene, ocimene, ⁇ -humulene, linalool, p-cymene, camphene, 3-carene, R-pinene, and ⁇ -terpinene.
  • the one or more terpenes comprise ⁇ -myrcene, ⁇ -caryophyllene, ocimene, ⁇ -humulene, linalool, p-cymene, camphene, 3-carene, R-pinene, and ⁇ -terpinene.
  • Embodiment 19 The pharmaceutical composition of any one of embodiments 1-12, wherein the one or more terpenes comprise ⁇ -myrcene, ⁇ -caryophyllene, ocimene, ⁇ -pinene, ⁇ -humulene, linalool, p-cymene, camphene, 3-carene, R-pinene, and ⁇ -terpinene.
  • the one or more terpenes comprise ⁇ -myrcene, ⁇ -caryophyllene, ocimene, ⁇ -pinene, ⁇ -humulene, linalool, p-cymene, camphene, 3-carene, R-pinene, and ⁇ -terpinene.
  • Embodiment 20 The pharmaceutical composition of any one of embodiments 1-19, wherein the one or more terpenes comprise ⁇ -myrcene, and wherein the pharmaceutical composition comprises 1-100 mg, 20-80 mg, 30-60 mg, 40-50 mg, 1-10 mg, 1.5-7.5 mg, or 2-5 mg of ⁇ -myrcene per dose.
  • Embodiment 21 The pharmaceutical composition of any one of embodiments 1-19, wherein the one or more terpenes comprise ⁇ -myrcene, and wherein the pharmaceutical composition comprises about: 1 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.1 mg, 2.2 mg, 2.3 mg, 2.4 mg, 2.5 mg, 2.6 mg, 2.7 mg, 2.8 mg, 2.9 mg, 3 mg, 3.1 mg, 3.2 mg, 3.3 mg, 3.4 mg, 3.5 mg, 3.6 mg, 3.7 mg, 3.8 mg, 3.9 mg, 4 mg, 4.5 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, or 10 mg of ⁇ -myrcene per dose.
  • Embodiment 22 The pharmaceutical composition of any one of embodiments 1-19, wherein the one or more terpenes comprise ⁇ -myrcene, and wherein the pharmaceutical composition comprises about: 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, or 60 mg of ⁇ -myrcene per dose.
  • Embodiment 23 The pharmaceutical composition of any one of embodiments 1-19, wherein the one or more terpenes comprise ⁇ -myrcene, and wherein the pharmaceutical composition comprises 1.5-7.5 mg of ⁇ -myrcene per dose.
  • Embodiment 24 The pharmaceutical composition of any one of embodiments 1-19, wherein the one or more terpenes comprise ⁇ -myrcene, and wherein the pharmaceutical composition comprises 30-60 mg of ⁇ -myrcene per dose.
  • Embodiment 25 The pharmaceutical composition of any one of embodiments 1-24, wherein the one or more terpenes comprise ⁇ -caryophyllene, and wherein the pharmaceutical composition comprises 1-20 mg, 2-10 mg, 2.5-5 mg, or 3-8 mg of ⁇ -caryophyllene per dose.
  • Embodiment 26 The pharmaceutical composition of any one of embodiments 1-24, wherein the one or more terpenes comprise ⁇ -caryophyllene, and wherein the pharmaceutical composition comprises about 1 mg, 1.5 mg, 2 mg, 2.25 mg, 2.5 mg, 2.75 mg, 3 mg, 3.1 mg, 3.2 mg, 3.3 mg, 3.4 mg, 3.5 mg, 3.6 mg, 3.7 mg, 3.8 mg, 3.9 mg, 4 mg, 4.25 mg, 4.5 mg, 4.75 mg, 5 mg, 5.5 mg, 6 mg, 6.5 mg, 7 mg, 7.5 mg, 7.6 mg, 8 mg, 9 mg, 10 mg, 12.5 mg, 15 mg, or 20 mg of ⁇ -caryophyllene per dose.
  • Embodiment 27 The pharmaceutical composition of any one of embodiments 1-24, wherein the one or more terpenes comprise ⁇ -caryophyllene, and wherein the pharmaceutical composition comprises 2.5-5 mg of ⁇ -caryophyllene per dose.
  • Embodiment 28 The pharmaceutical composition of any one of embodiments 1-27, wherein the one or more terpenes comprise ocimene, and wherein the pharmaceutical composition comprises 1-20 mg, 2-10 mg, 2.3-4.7 mg, or 3-8 mg of ocimene per dose.
  • Embodiment 29 The pharmaceutical composition of any one of embodiments 1-27, wherein the one or more terpenes comprise ocimene, and wherein the pharmaceutical composition comprises about 1 mg, 1.1 mg, 1.5 mg, 2 mg, 2.1 mg, 2.3 mg, 2.5 mg, 2.75 mg, 3 mg, 3.1 mg, 3.2 mg, 3.3 mg, 3.4 mg, 3.5 mg, 3.6 mg, 3.7 mg, 3.8 mg, 3.9 mg, 4 mg, 4.2 mg, 4.5 mg, 4.7 mg, 5 mg, 5.5 mg, 6 mg, 6.5 mg, 7 mg, 7.5 mg, 7.6 mg, 8 mg, 9 mg, 10 mg, 12.5 mg, 15 mg, or 20 mg of ocimene per dose.
  • Embodiment 30 The pharmaceutical composition of any one of embodiments 1-27, wherein the one or more terpenes comprise ocimene, and wherein the pharmaceutical composition comprises 2.3-4.7 mg of ocimene per dose.
  • Embodiment 31 The pharmaceutical composition of any one of embodiments 1-30, wherein the one or more terpenes comprise ⁇ -pinene, and wherein the pharmaceutical composition comprises 0.1-10 mg, 0.5-5 mg, or 1.1-2.1 mg of ⁇ -pinene per dose.
  • Embodiment 32 The pharmaceutical composition of any one of embodiments 1-30, wherein the one or more terpenes comprise ⁇ -pinene, and wherein the pharmaceutical composition comprises about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.1 mg, 2.2 mg, 2.3 mg, 2.4 mg, 2.5 mg, 2.75 mg, 3 mg, 3.5 mg, 4 mg, 4.5 mg, 5 mg, 7.5 mg, or 10 mg of ⁇ -pinene per dose.
  • Embodiment 33 The pharmaceutical composition of any one of embodiments 1-30, wherein the one or more terpenes comprise ⁇ -pinene, and wherein the pharmaceutical composition comprises 1.1-2.1 mg of ⁇ -pinene per dose.
  • Embodiment 34 The pharmaceutical composition of any one of embodiments 1-33, wherein the one or more terpenes comprise ⁇ -humulene, and wherein the pharmaceutical composition comprises 0.1-5 mg, 0.5-3.5 mg, or 0.8-1.6 mg of ⁇ -humulene per dose.
  • Embodiment 35 The pharmaceutical composition of any one of embodiments 1-33, wherein the one or more terpenes comprise ⁇ -humulene, and wherein the pharmaceutical composition comprises about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.1 mg, 2.2 mg, 2.3 mg, 2.4 mg, 2.5 mg, 2.6 mg, 2.7 mg, 2.8 mg, 2.9 mg, 3 mg, 3.1 mg, 3.2 mg, 3.5 mg, 4 mg, 4.5 mg, or 5 mg of ⁇ -humulene per dose.
  • Embodiment 36 The pharmaceutical composition of any one of embodiments 1-33, wherein the one or more terpenes comprise ⁇ -humulene, and wherein the pharmaceutical composition comprises 0.8-1.6 mg of ⁇ -humulene per dose.
  • Embodiment 37 The pharmaceutical composition of any one of embodiments 1-36, wherein the one or more terpenes comprise linalool, and wherein the pharmaceutical composition comprises 0.1-2 mg, 0.2-1.5 mg, or 0.3-0.9 mg of linalool per dose.
  • Embodiment 38 The pharmaceutical composition of any one of embodiments 1-36, wherein the one or more terpenes comprise linalool, and wherein the pharmaceutical composition comprises about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, or 2 mg of linalool per dose.
  • Embodiment 39 The pharmaceutical composition of any one of embodiments 1-36, wherein the one or more terpenes comprise linalool, and wherein the pharmaceutical composition comprises 0.3-0.9 mg of linalool per dose.
  • Embodiment 40 The pharmaceutical composition of any one of embodiments 1-39, wherein the one or more terpenes comprise p-cymene, and wherein the pharmaceutical composition comprises 0.1-20 mg, 0.25-10 mg, 5-10 mg, or 0.5-0.9 mg of p-cymene per dose.
  • Embodiment 41 The pharmaceutical composition of any one of embodiments 1-39, wherein the one or more terpenes comprise p-cymene, and wherein the pharmaceutical composition comprises about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.5 mg, 3 mg, 4 mg, 5 mg, 5.5 mg, 6 mg, 6.5 mg, 6.75 mg, 7 mg, 7.1 mg, 7.2 mg, 7.3 mg, 7.4 mg, 7.5 mg, 8 mg, 9 mg, 10 mg, 12.5 mg, 15 mg or 20 mg of p-cymene per dose.
  • Embodiment 42 The pharmaceutical composition of any one of embodiments 1-39, wherein the one or more terpenes comprise p-cymene, and wherein the pharmaceutical composition comprises 0.5-0.9 mg of p-cymene per dose.
  • Embodiment 43 The pharmaceutical composition of any one of embodiments 1-42, wherein the one or more terpenes comprise camphene, and wherein the pharmaceutical composition comprises 0.01-2 mg, 0.02-1 mg, 0.03-0.5 mg, or 0.05 to 0.15 mg of camphene per dose.
  • Embodiment 44 The pharmaceutical composition of any one of embodiments 1-42, wherein the one or more terpenes comprise camphene, and wherein the pharmaceutical composition comprises about 0.01 mg, 0.02 mg, 0.03 mg, 0.04 mg, 0.05 mg, 0.06 mg, 0.07 mg, 0.08 mg, 0.09 mg, 0.1 mg, 0.15 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1 mg, 1.25 mg, 1.5 mg, 1.75 mg, or 2 mg of camphene per dose.
  • Embodiment 45 The pharmaceutical composition of any one of embodiments 1-42, wherein the one or more terpenes comprise camphene, and wherein the pharmaceutical composition comprises 0.05-0.15 mg of camphene per dose.
  • Embodiment 46 The pharmaceutical composition of any one of embodiments 1-45, wherein the one or more terpenes comprise cis-nerolidol, and wherein the pharmaceutical composition comprises 0.5-20 mg, 1-10 mg, or 1.5 to 5 mg of cis-nerolidol per dose.
  • Embodiment 47 The pharmaceutical composition of any one of embodiments 1-45, wherein the one or more terpenes comprise cis-nerolidol, and wherein the pharmaceutical composition comprises about 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.25 mg, 2.5 mg, 3 mg, 4 mg, 4.5 mg, 4.8 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg 10 mg, 15 mg, or 20 mg of cis-nerolidol per dose.
  • Embodiment 48 The pharmaceutical composition of any one of embodiments 1-45, wherein the one or more terpenes comprise cis-nerolidol, and wherein the pharmaceutical composition comprises 1.5-5 mg of cis-nerolidol per dose.
  • Embodiment 49 The pharmaceutical composition of any one of embodiments 1-48, wherein the one or more terpenes comprise terpinolene, and wherein the pharmaceutical composition comprises 0.5-10 mg, 1-5 mg, or 1.2 to 3 mg of terpinolene per dose.
  • Embodiment 50 The pharmaceutical composition of any one of embodiments 1-48, wherein the one or more terpenes comprise terpinolene, and wherein the pharmaceutical composition comprises about 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.25 mg, 2.5 mg, 3 mg, 4 mg, 4.5 mg, 4.8 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg 10 mg, 15 mg, or 20 mg of terpinolene per dose.
  • Embodiment 51 The pharmaceutical composition of any one of embodiments 1-48, wherein the one or more terpenes comprise terpinolene, and wherein the pharmaceutical composition comprises 1.2-3 mg of terpinolene per dose.
  • Embodiment 52 The pharmaceutical composition of any one of embodiments 1-51, wherein the one or more terpenes comprise isopulegol, and wherein the pharmaceutical composition comprises 0.1-5 mg, 0.5-3.5 mg, or 0.8 to 2.3 mg of isopulegol per dose.
  • Embodiment 53 The pharmaceutical composition of any one of embodiments 1-51, wherein the one or more terpenes comprise isopulegol, and wherein the pharmaceutical composition comprises about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.3 mg, 2.5 mg, 3 mg, 3.5 mg, 4 mg, 4.5 mg, 4.8 mg, or 5 mg of isopulegol per dose.
  • Embodiment 54 The pharmaceutical composition of any one of embodiments 1-51, wherein the one or more terpenes comprise isopulegol, and wherein the pharmaceutical composition comprises 0.8-2.3 mg of isopulegol per dose.
  • Embodiment 55 The pharmaceutical composition of any one of embodiments 1-54, wherein the one or more terpenes comprise caryophyllene oxide, and wherein the pharmaceutical composition comprises 0.1-5 mg, 0.5-3.5 mg, or 0.8 to 2.2 mg of caryophyllene oxide per dose.
  • Embodiment 56 The pharmaceutical composition of any one of embodiments 1-54, wherein the one or more terpenes comprise caryophyllene oxide, and wherein the pharmaceutical composition comprises about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.2 mg, 2.5 mg, 3 mg, 3.5 mg, 4 mg, 4.5 mg, 4.8 mg, or 5 mg of caryophyllene oxide per dose.
  • Embodiment 57 The pharmaceutical composition of any one of embodiments 1-54, wherein the one or more terpenes comprise caryophyllene oxide, and wherein the pharmaceutical composition comprises 0.8-2.2 mg of caryophyllene oxide per dose.
  • Embodiment 58 The pharmaceutical composition of any one of embodiments 1-57, wherein the one or more terpenes comprise ⁇ -limonene, and wherein the pharmaceutical composition comprises 0.1-5 mg, 0.5-3.5 mg, or 0.8 to 1.6 mg of ⁇ -limonene oxide per dose.
  • Embodiment 59 The pharmaceutical composition of any one of embodiments 1-57, wherein the one or more terpenes comprise ⁇ -limonene, and wherein the pharmaceutical composition comprises about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.2 mg, 2.5 mg, 3 mg, 3.5 mg, 4 mg, 4.5 mg, 4.8 mg, or 5 mg of ⁇ -limonene per dose.
  • Embodiment 60 The pharmaceutical composition of any one of embodiments 1-57, wherein the one or more terpenes comprise ⁇ -limonene, and wherein the pharmaceutical composition comprises 0.8-1.6 mg of ⁇ -limonene per dose.
  • Embodiment 61 The pharmaceutical composition of any one of embodiments 1-60, wherein the one or more terpenes comprise geraniol, and wherein the pharmaceutical composition comprises 0.1-3 mg, 0.2-1.5 mg, or 0.4 to 0.9 mg of geraniol per dose.
  • Embodiment 62 The pharmaceutical composition of any one of embodiments 1-60, wherein the one or more terpenes comprise geraniol, and wherein the pharmaceutical composition comprises about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.2 mg, 2.5 mg, or 3 mg of geraniol per dose.
  • Embodiment 63 The pharmaceutical composition of any one of embodiments 1-60, wherein the one or more terpenes comprise geraniol, and wherein the pharmaceutical composition comprises 0.4-0.9 mg of geraniol per dose.
  • Embodiment 64 The pharmaceutical composition of any one of embodiments 1-63, wherein the one or more terpenes comprise guaiol, and wherein the pharmaceutical composition comprises 0.1-5 mg, 0.2-3.5 mg, or 0.4 to 3.2 mg of guaiol per dose.
  • Embodiment 65 The pharmaceutical composition of any one of embodiments 1-63, wherein the one or more terpenes comprise guaiol, and wherein the pharmaceutical composition comprises about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.2 mg, 2.4, 2.5 mg, 2.75, 3 mg, 3.2 mg, 3.5 mg, 4 mg, 4.5 mg, or 5 mg of guaiol per dose.
  • Embodiment 66 The pharmaceutical composition of any one of embodiments 1-63, wherein the one or more terpenes comprise guaiol, and wherein the pharmaceutical composition comprises 0.4-3.2 mg of guaiol per dose.
  • Embodiment 67 The pharmaceutical composition of any one of embodiments 1-66, wherein the one or more terpenes comprise ⁇ -bisobolol, and wherein the pharmaceutical composition comprises 0.1-3 mg, 0.2-1.5 mg, or 0.3 to 0.7 mg of ⁇ -bisobolol per dose.
  • Embodiment 68 The pharmaceutical composition of any one of embodiments 1-66, wherein the one or more terpenes comprise ⁇ -bisobolol, and wherein the pharmaceutical composition comprises about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.2 mg, 2.5 mg, or 3 mg of ⁇ -bisobolol per dose.
  • Embodiment 69 The pharmaceutical composition of any one of embodiments 1-66, wherein the one or more terpenes comprise ⁇ -bisobolol, and wherein the pharmaceutical composition comprises 0.3-0.7 mg of ⁇ -bisobolol per dose.
  • Embodiment 70 The pharmaceutical composition of any one of embodiments 1-69, wherein the one or more terpenes comprise 3-carene, and wherein the pharmaceutical composition comprises 0.1-3 mg, 0.2-1.5 mg, or 0.4 to 0.9 mg of 3-carene per dose.
  • Embodiment 71 The pharmaceutical composition of any one of embodiments 1-69, wherein the one or more terpenes comprise 3-carene, and wherein the pharmaceutical composition comprises about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.2 mg, 2.5 mg, or 3 mg of 3-carene per dose.
  • Embodiment 72 The pharmaceutical composition of any one of embodiments 1-69, wherein the one or more terpenes comprise 3-carene, and wherein the pharmaceutical composition comprises 0.4-0.9 mg of 3-carene per dose.
  • Embodiment 73 The pharmaceutical composition of any one of embodiments 1-72, wherein the one or more terpenes comprise ⁇ -pinene, and wherein the pharmaceutical composition comprises 0.1-5 mg, 0.3-3 mg, or 0.6 to 2.0 mg of ⁇ -pinene per dose.
  • Embodiment 74 The pharmaceutical composition of any one of embodiments 1-72, wherein the one or more terpenes comprise ⁇ -pinene, and wherein the pharmaceutical composition comprises about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.2 mg, 2.4, 2.5 mg, 2.75, 3 mg, 3.2 mg, 3.5 mg, 4 mg, 4.5 mg, or 5 mg of ⁇ -pinene per dose.
  • Embodiment 75 The pharmaceutical composition of any one of embodiments 1-72, wherein the one or more terpenes comprise ⁇ -pinene, and wherein the pharmaceutical composition comprises 0.6-2.0 mg of ⁇ -pinene per dose.
  • Embodiment 76 The pharmaceutical composition of any one of embodiments 1-75, wherein the one or more terpenes comprise ⁇ -terpinene, and wherein the pharmaceutical composition comprises 0.05-1.6 mg, 0.1-0.8 mg, or 0.2 to 0.4 mg of ⁇ -terpinene per dose.
  • Embodiment 77 The pharmaceutical composition of any one of embodiments 1-75, wherein the one or more terpenes comprise ⁇ -terpinene, and wherein the pharmaceutical composition comprises about 0.05 mg, 0.06 mg, 0.07 mg, 0.08 mg, 0.09 mg, 0.1 mg, 0.11 mg, 0.12 mg, 0.13 mg, 0.14 mg, 0.15 mg, 0.16 mg, 0.17 mg, 0.18 mg, 0.19 mg, 0.20 mg, 0.21 mg, 0.22 mg, 0.23 mg, 0.24 mg, 0.25 mg, 0.26 mg, 0.27 mg, 0.28 mg, 0.29 mg, 0.3 mg, 0.31 mg, 0.32 mg, 0.33 mg, 0.34 mg, 0.35 mg, 0.36 mg, 0.37 mg, 0.38 mg, 0.39 mg, 0.4 mg, 0.45 mg, 0.5 mg, 0.55 mg, 0.6 mg, 0.75 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, or 1.6 mg of ⁇ -terpinene per dose.
  • Embodiment 78 The pharmaceutical composition of any one of embodiments 1-75, wherein the one or more terpenes comprise ⁇ -terpinene, and wherein the pharmaceutical composition comprises 0.2-0.4 mg of ⁇ -terpinene per dose.
  • Embodiment 79 The pharmaceutical composition of any one of embodiments 1-78, wherein the one or more terpenes comprise ⁇ -myrcene, ⁇ -caryophyllene, ocimene, ⁇ -pinene, ⁇ -humulene, or a combination thereof, and wherein the pharmaceutical composition comprises about 30-60 mg of the ⁇ -mycene, about 2.5-5 mg of the ⁇ -caryophyllene, about 2.3-4.7 mg of the ocimene, about 1.1-2.1 mg of the ⁇ -pinene, about 0.8-1.6 mg of the ⁇ -humulene, or a combination thereof per dose.
  • Embodiment 80 The pharmaceutical composition of any one of embodiments 1-78, wherein the one or more terpenes comprise ⁇ -myrcene, ⁇ -caryophyllene, ocimene, ⁇ -pinene, and ⁇ -humulene; and wherein the pharmaceutical composition comprises about 30-60 mg of the ⁇ -mycene, about 2.5-5 mg of the ⁇ -caryophyllene, about 2.3-4.7 mg of the ocimene, about 1.1-2.1 mg of the ⁇ -pinene, and about 0.8-1.6 mg of the ⁇ -humulene per dose.
  • Embodiment 81 The pharmaceutical composition of any one of embodiments 1-80, wherein the pharmaceutical composition is formulated as a liquid, a pill, a gel capsule, a vaporizable liquid, a vaporizable solid, a transdermal ointment or salve, or a transdermal patch.
  • Embodiment 82 The pharmaceutical composition of any one of embodiments 1-80, wherein the pharmaceutical composition is formulated as a liquid.
  • Embodiment 83 The pharmaceutical composition of embodiment 82, wherein the liquid comprises citric acid, blue agave, glycerine, one or more lorann oils, food coloring, or a combination thereof.
  • Embodiment 84 The pharmaceutical composition of embodiment 82, wherein the liquid comprises: (a) about 1% to 7% w/w citric acid; (b) about 40% to 49% w/w blue agave; (c) about 40% to 49% w/w glycerin; (d) about 0.1% to 1.5% w/w lorann oils; (e) about 0.01 to 0.4% food coloring; (f) or a combination thereof.
  • Embodiment 85 The pharmaceutical composition of embodiment 82, wherein the liquid comprises: (a) about 1% to 7% w/w citric acid; (b) about 40% to 49% w/w blue agave; (c) about 40% to 49% w/w glycerin; (d) about 0.1% to 1.5% w/w lorann oils; and (e) about 0.01 to 0.4% food coloring.
  • Embodiment 86 The pharmaceutical composition of embodiment 82, wherein the liquid comprises: (a) about 3-5% w/w citric acid; (b) about 45-49% w/w blue agave; (c) about 45-49% w/w glycerin; (d) about 0.7-0.9% w/w lorann oils; and (e) about 0.1-0.3% food coloring.
  • Embodiment 87 The pharmaceutical composition of any one of embodiments 1-86, for use in the treatment of opioid addiction.
  • Embodiment 88 The pharmaceutical composition of any one of embodiments 1-86, for use in the treatment of pain.
  • Embodiment 89 The pharmaceutical composition of any one of embodiments 1-86, for use in the treatment of chemotherapy-induced nausea and vomiting.
  • Embodiment 90 A method of treating opioid addition, the method comprising administering an effective amount of a pharmaceutical composition comprising one or more cannabinoids to a subject in need thereof.
  • Embodiment 91 The method of embodiment 90, wherein the pharmaceutical composition is the pharmaceutical composition of any one of embodiments 1-86.
  • Embodiment 92 The method of embodiment 90 or 91, wherein the pharmaceutical composition is administered every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours.
  • Embodiment 93 The method of embodiment 90 or 91, wherein the pharmaceutical composition is administered every 6, 8 or 12 hours.
  • Embodiment 94 The method of any one of embodiment 90-93, wherein the subjects opioid use decreases by at least 50% within 5 weeks of beginning treatment as determined by morphine equivalency of opioids used.
  • This example details the production of an exemplary cannabinoid formulation that can be used in the methods disclosed herein.
  • the final product is aliquoted to bottles, each containing about 5.5 oz.
  • a single dose is about 12 mL.
  • the final product can contain, for example, about 15-20 mg THC and about 10-12 mg CBD per dose.
  • the final product can also contain terpenes; for example, 30-60 mg 0-myrcene (e.g., about 45 mg), 2.5-5 mg ⁇ -caryophyllene (e.g., about 3.7 mg), 2.3-4.7 mg ocimene (e.g., about 3.5), 1.1-2.1 mg ⁇ -pinene (e.g., about 1.6), 0.8-1.6 mg ⁇ -humulene (e.g, about 1.2 mg), or a combination thereof.
  • Table 2 contains an exemplary recipe.
  • Cannabis was taxonomically divided into three species in the 1970s; C. indica, C. sativa , and C. ruderalis . Adding to the confusion, yet ultimately clarifying was the work of McPartland wherein he proved on a genetic basis that these were all the same species, just different subspecies. More importantly he found that C. sativa originated in India and should have been classified as C. indica; C. indica originated in Afghanistan and should have been identified as C. afghanica ; and C. ruderalis is most properly classified as C. sativa . Until this nomenclature is standardized comparing research results will be near impossible.
  • CBD cannabidiol
  • THC delta-9 tetrahydrocannabinol
  • the population of subjects in this study included 14 women and 11 men.
  • the average age of participants was about 55 years old, with the youngest being 21 and the oldest being 77.
  • the median age was about 58 years old.
  • 4 participants had a history of gynecologic or breast cancer; 11 participants have had spine surgery; 5 participants have had a hysterectomy; 4 participants reported hypertension; 2 participants reported coronary artery disease, 2 participants had diabetes; 11 participants used tobacco; 6 participants used alcohol; and 3 participants reported drug abuse.
  • a morphine equivalent calculation was adopted for this study to account for the varying opiates used by the study participants.
  • Hydrocodone alone was used by 9 participants; hydrocodone plus morphine sulfate was used by 1 participant; hydromorphone alone was used by 2 participants; hydromorphone plus methadone was used by 1 participant; oxycodone alone was used by 6 participants; oxycodone plus methadone was used by 1 participant; oxycodone plus morphine sulfate was used by 2 participants; and Percocet was used by 3 participants.
  • EXAMPLE 3 a Phase III Double-Blind, Randomized, Placebo Controlled (with Crossover) Trial of Medical Marijuana Versus Placebo for the Reduction of Opiate Consumption in Patients with Chronic Pain
  • THC delta-9-tetrahydrocannabinol
  • CBD cannabidiol
  • Cannabis can also be effective in treating seizures, anorexia, chronic pain, and nausea and vomiting that is associated with chemotherapy.
  • Cannabidiols may also have a therapeutic effect of inflammation, diabetes, cancer, and neurodegenerative diseases.
  • THC ingestion has been associated with less than desirable side effects such as agitation; panic disorder; depression and even psychosis.
  • Cannabis -based therapy As an alternative means of managing chronic and cancer-related pain.
  • Nabiximols not appearing to be superior when compared to placebo in controlling pain in cancer patients, cannabis may have efficacy for pain control.
  • a cannabis -opioid interaction may also result in improved pain control.
  • Cannabis contains at least 63 cannabinoids but two are best understood studied.
  • the first, delta-9 tetrahydrocannabinol (THC) is thought to be responsible for the psychoactive effects that are widely associated with cannabis .
  • the other main active component, cannabidiol (CBD) has no known psychoactive effect associated with its consumption but is thought to possibly provide anti-neoplastic, analgesic and antineuroleptic effects.
  • CBD cannabidiol
  • CBD binds as an antagonist to the cannabinoid receptor CB1 but the bond between THC and the same receptor is at least 100 times stronger.
  • CBD also antagonizes the action on the cannabinoid G protein-coupled receptor GPR55, which is thought to be responsible the different neuromodulatory actions as the CB1 receptor. Claims of the subjective effects associated with cannabis ingestion include improvement in mood; relaxation; and increased sensitivity. On the other hand THC ingestion has been associated with less than desirable adverse effects such as agitation; panic disorder; depression and even psychosis.
  • Cannabinoids can have an effect on serotonergic systems, including increasing cerebral production of 5-hydroxytryptamine (5-HT), serotonin while decreasing its uptake at the synapse level.
  • THC may also have dopaminergic antagonistic actions which may contribute to its beneficial profile regarding pain control.
  • phytocannabinoids such as cannabichromene (CBC), cannabigerol (CBG) as well as a number of terpenoids may contribute its analgesic effect.
  • CBD, cannabinol (CBN),CBC and CBG can have anti-inflammatory and analgesic effects over and beyond that associated with THC.
  • B-caryophyllene may be a selective CB2 agonist and other terpenes such as linalool and ⁇ -Pinene may have analgesic and anti-inflamatory effects respectively.
  • Myrcene on the other hand may have analgesic effects mediated through an opioid-like action.
  • cannabis and it component parts may prevent opiate withdrawal and allow for the use of lesser amounts of opioids while preventing the development of tolerance.
  • cannabis Used in combination with opioid pain medications, cannabis can lower opioid side effects, cravings, and withdrawal severity, as well as enhance the analgesic effects of opioids, thereby allowing for lower doses and less risk of overdose.
  • THC is metabolized via the Cytochrome P450 pathway and more specifically it is thought that the CYP2C9 enzyme is responsible for the first pass metabolism of THC.
  • the CYP3A4 enzyme may also have a role in its metabolism.
  • Coumadin effect on prothrombin time (PT) is significantly enhanced by the use of THC/CBD.
  • Theophylline levels may be adversely affected. There have been reported adverse events when cannabis is used with sildenafil, including a myocardial infarction.
  • THC is a CNS depressant its use with alcohol, barbiturates, antihistamines, narcotics, and BZD, theoretically could amplify the effects of both drugs. It should be noted there has not been any clinical trial documenting these interactions. Similarly, adverse events need to be carefully documented. In this context cannabinoid receptors are not located in the brainstem as are opioid receptors and therefore do not have the associated risk of respiratory depression and death. Adverse effects including, but not limited to tachycardia and hypotension, anxiety and nervousness, hyperactivity, muscle relaxation, decreased bowel motility, and bronchodilatation have been documented.
  • cannabinoids The addictive potential of cannabinoids is thought to be lower than opiates and its derivatives as well as other frequently abused substances. Interestingly, as cannabinoids are stored in adipose, excretion takes place over a relatively long-time thus preventing precipitous declines in the plasma concentration and potentially explaining the lack of acute withdrawal symptoms associated with the cessation of cannabis use. Nevertheless, there have been documented symptoms associated with withdrawal including, but not limited to, nausea and vomiting, increased activity, nervousness, irritability, insomnia, and vasomotor symptoms.
  • Tetrahydrocannabinol Cannabidiol (THC:CBD) agave based syrup (20 mg THC/10 mg CBD) vs control agave-based syrup.
  • Each bottle will contain either 150-200 mg:100-120 mg (THC:CBD) in an agave based syrup with reconstituted terpene profile or the agave-based syrup alone.
  • THC:CBD 150-200 mg:100-120 mg
  • the emulsification process renders the material virtually odorless allowing for the patient to be blinded.
  • both are to be administered on a q6 to q8 hour basis (e.g., every 6 to 8 hours) by either direct administration or the syrup is to be mixed with 7-up with care being taken to chew the ice. If ineffective, the patient will double the dose. If there is no improvement then the patient will be crossed-over.
  • THC ingestion has been associated with adverse effects such as agitation; panic disorder; depression and even psychosis and all adverse events will be chronicled based on version 4.
  • Tetrahydrocannabinol Cannabidiol (THC:CBD) agave based syrup (15-20 mg THC/10-12 mg CBD) with reconstituted terpene profile versus control agave-based syrup.
  • Cannabis is intended for use as a psychoactive drug or as a medicine.
  • the main psychoactive part of cannabis is tetrahydrocannabinol (THC); it is one of at least 421 known compounds in the plant, including at least 61 other cannabinoids, such as cannabidiol (CBD), cannabinol (CBN), and tetrahydrocannabivarin (THCV).
  • CBD cannabidiol
  • CBN cannabinol
  • THCV tetrahydrocannabivarin
  • THC exerts its most prominent effects via its actions on two types of cannabinoid receptors, the CB1 receptor and the CB2 receptor, both of which are G-protein coupled receptors.
  • the CB1 receptor is found primarily in the brain as well as in some peripheral tissues, and the CB2 receptor is found primarily in peripheral tissues, but is also expressed in neuroglial cells
  • THC appears to alter mood and cognition through its agonist actions on the CB1 receptors, which inhibit a secondary messenger system (adenylate cyclase) in a dose dependent manner.
  • a secondary messenger system adenylate cyclase
  • CBlreceptor antagonist SR141716A rimonabant
  • SR141716A a selective CBlreceptor antagonist
  • THC indirectly increases dopamine release and produces psychotropic effects.
  • Cannabidiol also acts as an allosteric modulator of the mu and delta opioid receptors.
  • THC also potentiates the effects of the glycine receptors. The role of these interactions in the “marijuana high” remains elusive.
  • A9-THC is metabolized in the liver by microsomal hydroxylation and oxidation catalyzed by enzymes of cytochrome P450 (CYP) complex.
  • the average plasma clearance rates have been reported to be 11.8+3 L/hour for women and 14.9+3.7 L/hour for men.
  • Others have determined approximately 36 L/hour for na ⁇ ve cannabis users and 60 L/hour for regular cannabis users. More than 65% of cannabis is excreted in the feces and approximately 20% is excreted in urine. Most of the cannabis (80-90%) is excreted within 5 days as hydroxylated and carboxylated metabolites.
  • THCCOOH is the primary glucuronide conjugate in urine
  • 11-OH-THC is the predominant form in feces. Since A9-THC is extremely soluble in lipids, it results in tubular re-absorption, leading to low renal excretion of unchanged drug. Urinary excretion half-life of THCCOOH was observed to be approximately 30 hours after seven days and 44-60 hours after twelve days of monitoring.
  • the syrup is prepared using CO2 extracted THC which is then decarboxylated.
  • the syrup is composed of agave syrup, glycerin, citric acid, lecithin, THC/CBD oil, coloring and flavoring.
  • Each bottle marked on the sides in 12 millimeter increments, will contain a total of 150-200 mg of THC and approximately 100-120 mg of CBD and will provide ten doses of medicine.
  • the placebo will be the identical mixture without the addition of THC/CBD oil.
  • the patient will ingest 12 ml of either placebo or medicinal cannabis containing approximately 15-20 mg of THC and 10-12 mg CBD with the plant-specific terpenes reconsituted on a QID basis.
  • the patients will be allowed to double the dose if symptoms to do not resolve.
  • Short-term adverse effects include alterations in short-term memory, sense of time, sensory perception, attention span, problem solving, verbal fluency, reaction time, and psychomotor control. Some users report positive feelings such as mild euphoria and relaxation, while others, particularly na ⁇ ve users, report anxiety, paranoia, and panic reactions. Depression and anxiety have also been reported as short-term adverse events.
  • the short-term effects of marijuana last approximately 1-4 hours, depending on potency of the marijuana, the route of administration, and the tolerance of the user.
  • adverse cardiac events including arrhythmias associated with a prolonged Q-T interval; hypertension and hypotension; tachycardia; and myocardial infarction.
  • a 9-THC is metabolized in the liver by microsomal hydroxylation and oxidation catalyzed by enzymes of cytochrome P450 (CYP) complex.
  • CYP cytochrome P450
  • any drug that is similarly metabolized may be affected.
  • Particular attention must be given to warfarin or similar products; tadalafil or similar products; and anti-depressants.
  • Patients will be randomized using a computer based randomization program off-site and overseen by the independent observer. Patients will start the study within 2 days of filling their opiate prescription and verification through the Nevada State Prescription Monitoring Program that the patient is receiving narcotics from only a single source.
  • the total morphine milligram equivalents (MME) used weekly by the subject will be calculated based on the CDC conversion table. Subjects will be given a diary to record time and amount of study medication used on a daily basis in addition to recording any adverse events. Diaries will be collected weekly. Patients will be given physician phone number in order to report any adverse event.
  • MME total morphine milligram equivalents
  • Week 1 Patients are to use syrup (A or B) as directed on a q 6 hour basis and use their opiates only for breakthrough pain. The patient will be seen at the end of each week and a pill count will be done to determine the quantity of opiate (MME) consumed by the subject and recorded.
  • MME opiate
  • Weeks 2-7 At the end of week 2 if there has been no improvement as determined by at least a 20% reduction in total MME used compared to the baseline, the patient will crossed over and continued on the new syrup for a minimum of two additional weeks and if no reduction of at least 20% in total MME study treatment will be discontinued. If the patient's consumption of MME decreases by more than 20% within the first two weeks after initial drug assignment or after two weeks after being crossed-over, the patient will continue on the study drug for at least 4 additional weeks. The patient will be followed through the end of the study with collection of all study data.
  • the MME calculated at study entry, weekly and then at completion will be used to determine treatment course as well as the success or failure of the study drug.
  • the patients will complete a daily medication and toxicity diary and will be assessed weekly.
  • Amount of opiate consumed by pill count and MME will be recorded in the medication diary and by the physicians conducting the study.
  • the primary outcome is the complete elimination of opiate used to control the subject's symptoms.
  • Secondary outcome is the percentage reduction of opiate used to control the subject's symptoms as measured by pill count and MME.
  • the duration of the study will be 4 weeks at a minimum unless subject withdraws voluntarily or is caused to withdraw secondary to an adverse event deemed severe enough either by the patient or treating physician to warrant the subject's withdrawal from the protocol prescribed treatment plan.
  • An adverse event is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease that occurs in a patient administered a medical treatment, whether the event is considered related or unrelated to the medical treatment.
  • CTCAE Common Terminology Criteria for Adverse Events
  • SAE Serious Adverse Event
  • An AE report may need to reach multiple destinations. All expedited AEs will be reported to the IRB or the supervising body overseeing this study. Reporting will be modeled after AdEERS submissions. All adverse reactions will be immediately directed to the Study Chair for further action.
  • overdose of aprepitant is considered an SAE by the manufacturer. In the event that there is an overdose of aprepitant, report the overdose and any clinical consequences that occur in association with an overdose.
  • Expedited Reports are to be submitted to the study Chair and the IRB using reports similar to the AdEERS.
  • the overall objective of this study is to evaluate the probability of stopping opioid use within 5 weeks for patients diagnosed with chronic pain and treated with THC/CBD compared to those receiving placebo.
  • the subjects enrolled into this study will receive either daily THC/CBD or a placebo.
  • the study treatments will be sequentially allocated from predetermined lists consisting of randomly permuted study treatments within blocks. This allocation procedure will tend to allocate each of the study regimens to nearly an equal number of the enrollees. Other than blocking the treatments, the randomization procedure will not be otherwise constrained to provide an equal number of subjects in each treatment group.
  • the randomized treatment for each individual will remain concealed unless there arises a need for emergency unblinding. Emergency unblinding occurs when the appropriate clinical care of the subject requires knowledge of her study treatment.
  • the study's Principle Investigator will be responsible for reviewing and approving requests for emergency unblinding. An independent statistician will be responsible for revealing the study treatment.
  • Primary efficacy endpoint cessation of opioids for at least 7 days as determined by the treating physician.
  • CCAE Common Terminology Criteria for Adverse Events
  • the target enrollment for this study is 64 subjects.
  • the estimated accrual rate is 6 subjects per month. At this rate the enrollment period for this study is expected to require at most 1 year.
  • the target sample size will be increased by 2 subjects for each subject who withdraws from the study prior to completing at least 4 weeks of treatment or cannot be adequately evaluated for opioid usage.
  • THC/CBD does not increase the probability of stopping opioids within 5 weeks of starting THC/CBD compared to placebo.
  • the type I error for the primary efficacy hypothesis will be 0.025 for a one-tail test.
  • a logistic model will be used to assess whether the subject's initial morphine equivalency dose (MED), age or other clinical or demographic factors are treatment effect modifiers.
  • MED initial morphine equivalency dose
  • age or other clinical or demographic factors are treatment effect modifiers.
  • a linear mixed model will be used to model the patients' weekly morphine equivalency dose over time for women randomized to placebo vs those randomized to THC.
  • this design provides 82% chance of rejecting the primary null hypothesis for efficacy when the true probabilities of stopping opioids within 5 weeks are 5% and 35% for placebo and active, respectively.
  • Interim and final reports will include an accounting of all subjects registered onto the study, regardless of their eligibility status or compliance to their assigned treatment.
  • the Data Monitoring Committee (DMC) is responsible for reviewing the results of interim analyses. The decision to terminate accrual to the study or to release study results early includes consideration of adverse events, treatment compliance, as well as results from external studies.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Addiction (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Psychiatry (AREA)
  • Botany (AREA)
  • Otolaryngology (AREA)
  • Pain & Pain Management (AREA)
  • Hospice & Palliative Care (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present disclosure relates to cannabinoid-based therapeutics, and their use in treating pain, e.g., chronic pain. The present disclosure also relates to cannabinoid-based therapeutics, and their use in treating opioid addiction.

Description

    CROSS-REFERENCE
  • This application is a continuation of U.S. application Ser. No. 16/971,781, filed Aug. 21, 2020, which is a National Stage Application of International Application No. PCT/US2019/019465, filed Feb. 25, 2019, which claims the benefit of U.S. Provisional Application No. 62/634,547, filed Feb. 23, 2018, the disclosures of which are incorporated herein by reference in their entirety.
  • BACKGROUND OF THE INVENTION
  • There is a need in the art for methods and compositions to manage pain, e.g., chronic pain. There is also a need in the art for methods and compositions for treating opioid addiction.
  • SUMMARY OF THE INVENTION
  • Disclosed herein are pharmaceutical compositions comprising: tetrahydrocannabinol (THC) and cannabidiol (CBD) in a THC:CBD ratio of from 1:1.5 to 3:1 by weight; and one or more terpenes. In some embodiments, the THC:CBD ratio is from 1.5:1 to 2:1. In some embodiments, the THC:CBD ratio is about 1.5:1.
  • In some embodiments, the pharmaceutical composition comprises about 15-20 mg tetrahydrocannabinol (THC) per dose. In some embodiments, the pharmaceutical composition comprises 10-12 mg cannabidiol (CBD).
  • In some embodiments, the one or more terpenes comprise β-myrcene, β-caryophyllene, ocimene, α-pinene, α-humulene, linalool, p-cymene, camphene, cis-nerolidol, terpinolene, isopulegol, caryophyllene oxide, δ-limonene, geraniol, guaiol, α-bisabolol, 3-carene, β-pinene, γ-terpinene, or a combination thereof. In some embodiments, rein the one or more terpenes comprise β-myrcene, β-caryophyllene, ocimene, α-pinene, and α-humulene.
  • In some embodiments, the one or more terpenes comprise β-myrcene, and wherein the pharmaceutical composition comprises 30-60 mg of β-myrcene per dose.
  • In some embodiments, the one or more terpenes comprise β-caryophyllene, and wherein the pharmaceutical composition comprises 2.5-5 mg of β-caryophyllene per dose.
  • In some embodiments, the one or more terpenes comprise ocimene, and wherein the pharmaceutical composition comprises 2.3-4.7 mg of ocimene per dose.
  • In some embodiments, the one or more terpenes comprise α-pinene, and wherein the pharmaceutical composition comprises 1.1-2.1 mg of α-pinene per dose.
  • In some embodiments, the one or more terpenes comprise α-humulene, and wherein the pharmaceutical composition comprises 0.8-1.6 mg of α-humulene per dose.
  • In some embodiments, the one or more terpenes comprise β-myrcene, β-caryophyllene, ocimene, α-pinene, and α-humulene; and wherein the pharmaceutical composition comprises about 30-60 mg of the β-mycene, about 2.5-5 mg of the β-caryophyllene, about 2.3-4.7 mg of the ocimene, about 1.1-2.1 mg of the α-pinene, and about 0.8-1.6 mg of the α-humulene per dose.
  • In some embodiments, the pharmaceutical composition is formulated as a liquid, a pill, a gel capsule, a vaporizable liquid, a vaporizable solid, a transdermal ointment or salve, or a transdermal patch.
  • In some embodiments, the pharmaceutical composition is formulated as a liquid. In some embodiments, the liquid comprises citric acid, blue agave, glycerine, one or more lorann oils, food coloring, or a combination thereof.
  • In some embodiments, the liquid comprises: about 1% to 7% w/w citric acid; about 40% to 49% w/w blue agave; about 40% to 49% w/w glycerin; about 0.1% to 1.5% w/w lorann oils; about 0.01 to 0.4% food coloring; or a combination thereof. In some embodiments, the liquid comprises: about 3-5% w/w citric acid; about 45-49% w/w blue agave; about 45-49% w/w glycerin; about 0.7-0.9% w/w lorann oils; and about 0.1-0.3% food coloring.
  • In some embodiments, the pharmaceutical composition is for use in the treatment of opioid addiction.
  • In some embodiments, the pharmaceutical composition is for use in the treatment of pain.
  • In some embodiments, the pharmaceutical composition is for use in the treatment of chemotherapy-induced nausea and vomiting.
  • Also disclosed herein are methods of treating opioid addition, the methods comprising administering an effective amount of a pharmaceutical composition comprising one or more cannabinoids to a subject in need thereof. The pharmaceutical composition can be any pharmaceutical composition disclosed herein.
  • In some embodiments, the pharmaceutical composition is administered every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours.
  • In some embodiments, the pharmaceutical composition is administered every 6, 8 or 12 hours.
  • In some embodiments, the subjects opioid use decreases by at least 50% within 5 weeks of beginning treatment as determined by morphine equivalency of opioids used.
  • INCORPORATION BY REFERENCE
  • All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. In the event that a term incorporated by reference conflicts with a term defined herein, this specification shall control.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:
  • FIG. 1 a &b illustrates weekly pill counts in chart form (FIG. 1 a ) and graph form with regression analysis (FIG. 1 b ).
  • FIG. 2 a &b illustrates weekly pill counts in morphine equivalents in tabular form (FIG. 2 a ) and graph form with regression analysis (FIG. 2 b ).
  • DETAILED DESCRIPTION OF THE INVENTION
  • The present disclosure relates to therapeutics, and more especially the use of cannabinoid-based therapeutics, for use in treating those known to have chronic pain. In some cases, the chronic pain may have been treated using opiates. The present disclosure also relates to cannabinoid-based therapeutics for use in treating opioid addiction.
  • INTRODUCTION
  • In the United States the estimated total annual cost of pain-related health is approximately $600 billion and perhaps this figure is even higher for the nations in European Union (EU). This estimate includes the actual costs related to the medical care as well as the economic losses which contribute to approximately one-half of these costs. Economic losses include claimed disability, loss of productivity and lost wages. Medical care including physician time, hospitalization, surgical procedures, diagnostic testing and prescription drugs all contribute to the costs associated with the treatment of pain, as well the costs associated with the adverse effects associated with their utilization. Unfortunately, one of the adverse effects associated with prescription painkillers is death. Overdose deaths secondary to prescription opioids were five times higher in 2016 than 1999 and sales of these prescription drugs have quadrupled. That being said, the number of deaths dues to prescription opioids has remained relative stable at approximately 14,000 to 16,000 deaths per year. Much of the increase in mortality related to opioid consumption is due the rapid rise in those associated with the use of synthetic opioids. In states with either medical marijuana or both medical and retail marijuana programs in place there was a 24.8% lower mean annual opioid overdose mortality rate (95% CI, −37.5% to −9.5%: P=0.003) compared with states without medical marijuana laws.
  • Addressing the opiate crisis in this country has led to a number of studies being conducted using cannabis-based therapy as an alternative means of managing chronic and cancer-related pain. Despite Nabiximols not appearing to be statistically superior when compared to placebo in controlling pain in cancer patients, there are other randomized placebo controlled trials demonstrating the efficacy of using cannabis for pain control. There is also significant evidence that a cannabis-opioid interaction exists that results in improved pain control. All of the studies to date have either used pain scales or patient interview results to determine the success or failure of the cannabis intervention.
  • A group of physicians in Nevada, licensed to cultivate, produce and sell cannabis-related products and have recently undertaken a two phase II trials ran using a guava-based syrup with a THC:CBD ratio of 2:1 and at a 1:1 ratio containing only the flavored guava-based syrup. Each dose of syrup contained either 10 mg/ml of both delta-9-tetracannabinol (THC) and cannabidiol (CBD) or 20 mg of THC and 10 mg of CBD. As a proof of concept 25 patients in each group with a history of at least 3 years of chronic opiate use were enrolled in a single arm study with the endpoint being a 30% reduction of opiate intake determined by weekly pill count. 23 of the 25 patients reduced their opiate intake by greater than 50%. This provides an objective basis to evaluate the potential of cannabis to reduce the opiate consumption across the US.
  • The claimed beneficial medicinal effects associated with cannabis consumption are quite diverse and of long-standing. In 1889, some of these benefits were first described in the medical literature by Dr. E. A. Birch. Of the claims made, the most studied are in patients with multiple sclerosis, where a beneficial effect on muscle spasticity and pain are well-documented, but not necessarily as consistently as one might like. Cannabis has also been shown to be effective in treating seizures, anorexia, chronic pain, and nausea and vomiting that is associated with chemotherapy. There is some evidence that cannabidiols have a therapeutic effect of inflammation, chronic pain, diabetes, cancer, and neurodegenerative diseases.
  • To understand the underlying basis for the use of cannabinoids in the treatment of chronic pain it is imperative to understand their likely mechanisms of action. Cannabis contains at least 63 cannabinoids but two are best understood studied. The first, delta-9 tetrahydrocannabinol (THC), is responsible for the psychoactive effects that is widely associated with cannabis. The other main active component, cannabidiol (CBD), has no psychoactive effect associated with its consumption but is thought to provide anti-neoplastic, analgesic and antineuroleptic effects per the literature. Even though both cannabinoids are present in every plant, the interactions with the cerebral endocannabinoid receptor system are quite different. CBD binds as an antagonist to the cannabinoid receptor CB1 but the bond between THC and the same receptor is at least 100 times stronger. CBD also antagonizes the action on the cannabinoid G protein-coupled receptor GPR55, which is thought to be responsible the different neuromodulatory actions as the CB1 receptor. Claims of the subjective effects associated with cannabis ingestion include improvement in mood; relaxation; and increased sensitivity. On the other hand THC ingestion has been associated with less than desirable adverse effects such as agitation; panic disorder; depression and even psychosis.
  • Cannabinoids have an effect on serotonergic systems, including increasing cerebral production of 5-hydroxytryptamine (5-HT), serotonin while decreasing its uptake at the synapse level. THC has been found to have dopaminergic antagonistic actions which may contribute to its beneficial profile regarding pain control.
  • Other phytocannabinoids such as cannabichromene (CBC), cannabigerol (CBG) as well as a number of terpenoids likely contribute its analgesic effect. CBC and CBG have significant anti-inflamatory and analgesic effects over and beyond that associated with THC. B-caryophyllene has been shown to be a selective CB2 agonist and other terpenes such as linalool and a-Pinene have analgesic and anti-inflamatory effects respectively. Myrcene other the other hand has been shown to have analgesic effects mediated through an opioid-like action. This is an important development as it helps explain another avenue as to how cannabis and it component parts may prevent opiate withdrawal and allow for the use of lesser amounts of opioids while preventing the development of tolerance. Used in combination with opioid pain medications, cannabis can lower opioid side effects, cravings, and withdrawal severity, as well as enhance the analgesic effects of opioids, thereby allowing for lower doses and less risk of overdose.
  • As explained above the actions of THC, CBD, associated terpenes are potentially complementary and there is substantial evidence to suggest benefit of using together for patients with chronic pain.
  • Embodiments of the Disclosure
  • An embodiment of the present disclosure is the therapeutic compound for the use in treating chronic pain and like disorders and preferably in liquid form compromising a formulation including cannabinoids, but not limited to delta-9—tetrahydrocannabinol and cannabidiol. The compound may optionally include any terpene or terpinoid present in a cannabis plant. A subject suffering from chronic pain is orally administered a therapeutically effective amount of the compound so as to alleviate, cure or prevent the symptoms associated with chronic pain.
  • Another embodiment of the present disclosure is the therapeutic compound for the use in treating chronic pain and like disorders and preferably in a pill form compromising a formulation including cannabinoids, but not limited to delta-9-tetrahydrocannabinol and cannabidiol. The compound may optionally include any terpene or terpinoid present in a cannabis plant. A subject suffering from chronic pain is orally administered a therapeutically effective amount of the compound so as to alleviate, cure or prevent the symptoms associated with chronic pain
  • Another embodiment of the present disclosure is the therapeutic compound for the use in treating chronic pain and like disorders and preferably in suppository form compromising a formulation including cannabinoids, but not limited to delta-9-tetrahydrocannabinol and cannabidiol. The compound may optionally include any terpene or terpinoid present in a cannabis plant. A subject suffering from chronic pain is orally administered a therapeutically effective amount of the compound so as to alleviate, cure or prevent the symptoms associated with chronic pain
  • Another embodiment of the present disclosure is the therapeutic compound for the use in treating chronic pain and like disorders and preferably in capsule form compromising a formulation including cannabinoids, but not limited to delta-9-tetrahydrocannabinol and cannabidiol. The compound may optionally include any terpene or terpinoid present in a cannabis plant. A subject suffering from chronic pain is orally administered a therapeutically effective amount of the compound so as to alleviate, cure or prevent the symptoms associated with chronic pain.
  • Another embodiment of the present disclosure is the therapeutic compound for the use in treating chronic pain and like disorders and preferably in a transdermal form compromising a formulation including cannabinoids, but not limited to delta-9-tetrahydrocannabinol and cannabidiol. The compound may optionally include any terpene or terpinoid present in a cannabis plant. A subject suffering from chronic pain is transdermally administered a therapeutically effective amount of the compound so as to alleviate, cure or prevent the symptoms associated with chronic pain.
  • Another embodiment of the present disclosure is the therapeutic compound for the use in treating chronic pain and like disorders and preferably in an inhalable/nebulized form compromising a formulation including cannabinoids, but not limited to delta-9-tetrahydrocannabinol and cannabidiol. The compound may optionally include any terpene or terpinoid present in a cannabis plant. A subject suffering from chronic pain is inhaled in a therapeutically effective amount of the compound so as to alleviate, cure or prevent the symptoms associated with chronic pain
  • It shall be noted that the cannabinoid disclosed herein may include any of the identified cannabinoids, but not limited to THC (Tetrahydrocannabinol); THCA (Tetrahydrocannabinolic acid); CBD (Cannabidiol); CBDA (Cannabidiolic Acid); CBN (Cannabinol); CBG (Cannabigerol); CBC (Cannabichromene); CBL (Cannabicyclol); CBV (Cannabivarin); THCV (Tetrahydrocannabivarin); CBDV (Cannabidivarin); CBCV (Cannabichromevarin); CBGV (Cannabigerovarin); CBGM (Cannabigerol Monomethyl Ether); CBE (Cannabielsoin); CBT (Cannabicitran); (OTHC) 10-Oxo-delta-6a-tetrahydrocannabinol; (CBCF) Cannabichromanon; (CBF) Cannabifuran; Cannabiglendol; (CBR) Cannabiripsol; (CBT)Cannbicitran; (DCBF) Dehydrocannabifuran; (cis-THC) Delta-9-cis-tetrahydrocannabinol; (triOH-THC) Tryhydroxy-delta-9-tetrahydrocannabinol; and OH-iso-HHCV.
  • It shall also be noted that the terpene disclosed herein may, but is not limited to, any single or combination of the terpenes listed in table 1.
  • TABLE 1
    List of exemplary terpenes
    RI
    No. chemical name (DB1) formula MW
    1 Fusicocca-3,5-diene 1850 C20H32 272
    2 9-epi-Sclarene 1896 C20H32 272
    3 Laurenene 1903 C20H32 272
    4 Rimuene 1907 C20H32 272
    5 Isopimara-8,15-diene 1922 C20H32 272
    6 Cembrene 1938 C20H32 272
    7 Pimara-8,15-diene 1942 C20H32 272
    8 Sclarene 1943 C20H32 272
    9 Isohibaene 1944 C20H32 272
    10 Rosa-5,15-diene 1945 C20H32 272
    11 (E)-2,6-Dimethyl-10-(p-tolyl)- 1945 C20H30 270
    undeca-2,6-diene
    12 Isocembrene 1951 C20H32 272
    13 Beyerene 1951 C20H32 272
    14 Pimara-8(14),15-diene 1955 C20H32 272
    15 Cembrene A 1962 C20H32 272
    16 Labda-7,13,14-triene 1978 C20H32 272
    17 Isopimara-8(14),15-diene 1981 C20H32 272
    18 Isophyllocladene 1982 C20H32 272
    19 Dolabella-6,10,15-triene 1984 C20H32 272
    20 (Z)-Biformene 1988 C20H32 272
    21 Manool oxide 2007 C20H34O 290
    22 Geranyllinalool 2008 C20H32 272
    23 Isopimara-7,15-diene 2010 C20H32 272
    24 15-Kaurene 2011 C20H32 272
    25 Isopimara-8,15-diene 2016 C20H32 272
    26 Dolabradiene 2017 C20H32 272
    27 Trachylobane 2022 C20H32 272
    28 (E)-Biformene 2017 C20H32 272
    29 Cembrene C 2023 C20H32 272
    30 13-epi-Manoyl oxide 2023 C20H34O 290
    31 (E)-Labda-7,12,14-triene 2036 C20H32 272
    32 Phyllocladene 2042 C20H32 272
    33 Abietatriene 2046 C20H30 270
    34 16-Atisirene 2051 C20H32 272
    35 16-Kaurene 2056 C20H32 272
    36 Manool 2070 C20H32 272
    37 Aphidicol-15-ene 2073 C20H32 272
    38 Valpara-2,15-diene 2073 C20H32 272
    39 Abieta-7,13-diene 2084 C20H32 272
    40 Labda-7,14-dien-13-ol 2096 C20H34O 290
    41 Aphidicol-16-ene 2102 C20H32 272
    42 Isoabienol 2124 C20H34O 290
    43 Abieta-8(14),13(15)-diene 2152 C20H32 272
    44 (8a,12Z)-Abienol 2146 C20H34O 290
    45 Incensole 2193 C20H34O2 306
    46 Sclareol 2231 C20H36O2 308
    47 Labda-8(17),14-dien-6,13-diol 2248 C20H34O2 306
    48 Incensol acetate 2220 C22H36O3 348
    49 Verticilla-4(20),7,11-triene 2040 C20H32 272
    50 m-Camphorene 1947 C20H32 272
    51 p-Camphorene 1980 C20H32 272
    52 Cembrenol 2131 C20H34O 290
    53 Sterna-13-ene 2025 C20H32 272
    54 2-Allyl-4-methylphenol 1262 C10H12O 148
    55 8,9-Dehydrothymol acetate 1360 C12H14O2 190
    56 3,5,5-Trimethyl-4- 1200 C10H14O 150
    methylenecyclohex-2-enone
    57 Cabreuva oxide D 1467 C15H24O 220
    58 p-Isopropylbenzaldehyd 1220 C10H12O 148
    59 3-Methyl-4-(2,6,6- 1471 C14H22O 206
    trimethylcyclohex-2-enyl)-but-3-en-
    2-one
    60 2,6,6-Trimethyl-3-oxocyclohex-1- 1110 C10H14O2 166
    ene-1-carbaldehyde
    61 Isophorone 1100 C9H14O 138
    62 3,5,5-Trimethylcyclohex-3-enone 1027 C9H14O 138
    63 trans-Sabinyl acetate 1278 C12H16O2 192
    64 Nerol 1210 C10H18O 154
    65 3a-Hydroxy-1,8-cineol 1217 C10H18O2 170
    66 Carvone 1214 C10H14O 150
    67 Thymol methyl ether 1215 C11H16O 164
    68 Pulegone 1215 C10H16O 152
    69 Neral 1215 C10H16O 152
    70 p-Anisaldehyde 1218 C8H8O2 136
    71 Chavicol 1219 C9H10O 134
    72 2,3-Dehydro-1,4-cineol 1219 C10H16O 152
    73 trans-Isopulegone 1161 C10H16O 152
    74 Piperitone 1226 C10H16O 152
    75 1,4-Dimethoxy-2-methylbenzene 1226 C9H12O2 152
    76 Carvacrol methyl ether 1226 C11H16O 164
    77 Isobornyl formate 1228 C11H18O2 182
    78 2-Phenylethyl acetate 1230 C10H12O2 164
    79 (E)-Cinnamaldehyde 1234 C9H8O 132
    80 2,3-Dehydro-1,8-cineol 993 C10H16O 152
    81 2-Hydroxypinan-3-one 1235 C10H16O2 168
    82 Geraniol 1235 C10H18O 154
    83 Pseudodiosphenol 1245 C10H16O2 168
    84 cis-Chrysanthenyl acetate 1253 C12H18O2 194
    85 trans-Carvone epoxide 1243 C10H14O2 166
    86 cis-Sabinene hydrat acetate 1248 C12H20O2 196
    87 cis-Ethyl chrysanthemate 1251 C12H20O2 196
    88 trans-Sabinen hydrate acetate 1254 C12H20O2 196
    89 Citronellyl formate 1259 C11H20O2 184
    90 Perilla aldehyde 1260 C10H14O 150
    91 trans-Ethyl chrysanthemate 1260 C12H20O2 196
    92 trans-Anethol 1262 C10H12O 148
    93 Nonanoic acid 1263 C9H18O2 158
    94 Isopulegol acetate (Isomer 1) 1263 C12H20O2 196
    95 Methyl nerolate 1265 C11H18O2 182
    96 Safrol 1265 C10H10O2 162
    97 cis-Thiorose oxide 1265 C10H18S 170
    98 cis-Verbenyl acetate 1266 C12H18O2 194
    99 Thymol 1267 C10H14O 150
    100 Bornyl acetate 1270 C12H20O2 196
    101 Neomenthyl acetate 1263 C12H22O2 198
    102 Deca-2,4-dienal 1270 C10H16O 152
    103 Isopulegol acetate (Isomer 2) 1271 C12H20O2 196
    104 2-Undecanone 1273 C10H16O 152
    105 4,8-Dimethylnonanol 1276 C11H24O 172
    106 Diosphenol 1276 C10H16O2 168
    107 Isobornyl acetate 1276 C12H20O2 196
    108 Carvacrol 1278 C10H14O 150
    109 Thujopsadiene 1470 C15H22 202
    110 Sesamol 1280 C7H6O3 138
    111 Menthyl acetate 1280 C12H22O2 198
    112 Geranial 1244 C10H16O 152
    113 Geranyl formate 1284 C11H18O2 182
    114 trans-Thiorose oxide 1284 C10H18S 170
    115 2-Undecanol 1284 C11H24O 172
    116 p-Isopropylbenzyl alcohol 1285 C10H14O 150
    117 Sencyunolide 1672 C12H16O2 192
    118 trans-Pinocarvyl acetate 1287 C12H18O2 194
    119 2,3,6-Trimethylbenzaldehyde 1287 C10H12O 148
    120 Terpinen-4-ol acetate 1289 C12H20O2 196
    121 Chrysanthenone epoxide 1290 C10H14O2 166
    122 (E,E)-Deca-2,4-dienal 1291 C10H16O 152
    123 Puleganolide (Isomer 1) 1292 C10H16O2 168
    124 Dihydrocarveol acetate (Isomer 2) 1295 C12H20O2 196
    125 Isoascaridol 1295 C10H16O2 168
    126 Theaspirane (Isomer 1) 1299 C13H22O 194
    127 cis-Pinocarvyl acetate 1300 C12H18O2 194
    128 Dihydronaginata ketone 1300 C10H14O2 166
    129 Naginata ketone alcohol 1306 C10H14O3 182
    130 Puleganolide (Isomer 2) 1305 C10H16O2 168
    131 Methyl geranate 1306 C11H18O2 182
    132 Vinylguaiacol 1311 C9H10O2 150
    133 5-Acetoxylinalool 1303 C12H20O3 212
    134 Theaspirane (Isomer 2) 1313 C13H22O 194
    135 Chavicol acetate 1313 C11H12O2 176
    136 Myrtenyl acetate 1313 C12H18O2 194
    137 Dihydrocarveol acetate (Isomer 2) 1314 C12H20O2 196
    138 Apiol 1649 C12H14O4 222
    139 trans-Carvyl acetate 1318 C12H18O2 194
    140 Thymol acetate 1329 C12H16O2 192
    141 Menthothiophene 1330 C10H14S 166
    142 2,3,4-Trimethylbenzaldehyde 1331 C10H12O 148
    143 Eugenol 1331 C10H12O2 164
    144 cis-Dihydrocarvone epoxide 1333 C10H16O2 168
    145 Ethyl nerolat 1335 C12H20O2 196
    146 Fragranol 1201 C12H20O2 196
    147 7,8-Dihydro-b-ionone 1422 C13H22O 194
    148 8-Hydroxylinalool 1336 C10H18O2 170
    149 3,4-Dimethoxystyrene 1337 C10H12O2 164
    150 Citronellyl acetate 1337 C12H22O2 198
    151 trans-8-Mercapto-p-menthan-3-one 1340 C10H18OS 186
    152 Anhydroencecalinol 1640 C14H16O2 216
    153 Neryl acetate 1342 C12H20O2 196
    154 Dihydrocarveol acetate (Isomer 2) 1342 C12H20O2 196
    155 exo-Isocamphanyl acetate 1345 C12H20O2 196
    156 cis-Carvyl acetate 1345 C12H18O2 194
    157 (Z)-Ethyl cinnamate 1344 C11H12O2 176
    158 Chavibetol (m-Eugenol) 1346 C10H12O2 164
    159 4-Methoxyphenylethanol 1347 C9H12O2 152
    160 (E)-Anethol epoxide 1347 C10H12O2 164
    161 trans-Dihydrocarvone epoxide 1352 C10H16O2 168
    162 endo-Isocamphanyl acetate 1352 C12H20O2 196
    163 (E)-Methyl cinnamate 1354 C10H10O2 162
    164 cis-8-Mercapto-p-menthan-3-one 1356 C10H18OS 186
    165 Dihydrojasmone 1361 C10H14O2 166
    166 (E)-b-Damascenone 1363 C13H18O 190
    167 3-Allyl-1,4-dimethoxybenzene 1370 C11H14O2 178
    168 (Z)-Jasmone 1371 C11H16O 164
    169 Isobornyl propionate 1375 C13H22O2 210
    170 Ethyl geranate 1377 C12H20O2 196
    171 Methyl perillate 1381 C11H16O2 180
    172 (Z)-Isoeugenol 1381 C10H12O2 164
    173 Osmorhizol 1383 C11H14O2 178
    174 2-Dodecanol 1387 C12H26O 186
    175 1-Tetradecene 1387 C14H28 196
    176 Davanafuran 1394 C14H20O2 220
    177 Methyl 4-methoxyphenylacetate 1398 C10H12O3 180
    178 (E)-b-Damascone 1398 C13H20O 192
    179 trans-Carvyl propionate 1402 C13H20O2 208
    180 2,6-Dimethoxycymene 1402 C12H18O2 194
    181 Nerylacetone 1412 C13H22O 194
    182 2-Hydroxy-1,2-dihydrolavandulyl 1416 C12H22O3 214
    acetate
    183 (Z)-1,2-Dimethoxy-4- 1419 C11H14O2 178
    propenylbenzene
    184 (E)-Cinnamyl acetate 1420 C11H12O2 176
    185 Isobornyl isobutyrate 1424 C14H24O2 224
    186 Citronellyl propionate 1427 C13H24O2 212
    187 3,4-Dimethoxybenzaldehyde 1428 C9H10O3 166
    188 (E)-Isoeugenol 1429 C10H12O2 164
    189 cis-Carvyl propionate 1436 C13H20O2 208
    190 Massoialactone 1439 C10H16O2 168
    191 d-Undecanolide 1565 C11H20O2 184
    192 Nordavanone 1451 C11H18O2 182
    193 8-Dehydrothymol isobutyrate 1458 C14H18O2 218
    194 (E)-1,2-Dimethoxy-4- 1460 C11H14O2 178
    propenylbenzene
    195 Thymol isobutyrate 1462 C14H20O2 220
    196 Isobornyl butyrate 1462 C14H24O2 224
    197 3,4-Dimethoxybenzyl alcohol 1464 C9H12O3 168
    198 Sarisane 1466 C11H12O3 192
    199 2-Tridecanone 1477 C13H26O 198
    200 2-Tridecanol 1490 C13H28O 200
    201 Davana ether 1489 C15H22O2 234
    202 a-Campholenyl formate 1240 C11H18O2 182
    203 Chavibetyl acetate 1488 C12H14O3 206
    204 Homovanilline alcohol 1494 C9H12O3 168
    205 Davana ether (Isomer) 1507 C15H22O2 234
    206 Isobornyl isovalerate 1516 C15H26O2 238
    207 Citronellyl butyrate 1516 C14H26O2 226
    208 Elemicine 1522 C12H16O3 208
    209 Flavesone 1526 C14H20O4 252
    210 allo-Davanone 1539 C15H24O2 236
    211 Isodavanone 1545 C15H24O2 236
    212 Eupatoriochromene 1726 C13H16O3 220
    213 cis-Davanone 1557 C15H24O2 236
    214 Geranyl crotonate 1555 C14H22O2 222
    215 Diethylphthalate 1555 C12H14O4 222
    216 cis-8-Acetylthio-p-menthan-3-one 1559 C12H20O2S 228
    217 4-Allyl-2,6-dimethoxyphenol 1561 C11H14O3 194
    218 Sandela 1568 C16H28O 236
    219 trans-8-Acetylthio-p-mentan-3-one 1570 C12H20O2S 228
    220 (Z)-Asarone 1584 C12H16O3 208
    221 (Z)-3-Hexenyl benzoate 1545 C13H16O2 204
    222 Geranyl 2-methylbutyrate 1591 C15H26O2 238
    223 1,2-Diacetoxy-4-allylbenzene 1602 C13H14O4 234
    224 Leptospermone 1611 C15H22O4 266
    225 (Z)-Ethyl p-methoxycinnamate 1614 C12H14O3 206
    226 Butylphthalide 1616 C12H14O2 190
    227 (E)-Asarone 1636 C12H16O3 208
    228 (Z)-Butylidenphthalide 1644 C12H12O2 188
    229 6-Methoxythymol isobutyrate 1658 C15H22O3 250
    230 2-Pentadecanone 1688 C15H30O 226
    231 (E)-Ethyl p-methoxycinnamate 1711 C12H14O3 206
    232 (Z)-Ligustilide 1732 C12H14O2 190
    233 Heyderiol 2374 C22H30O4 358
    234 (E)-Ligustilide 1782 C12H14O2 190
    235 7,11-Dimethylheptadecane 1792 C19H40 268
    236 Avocadynofuran 1796 C17H26O 246
    237 Galaxolide 1838 C18H26O 258
    238 Traseolide 1840 C18H26O 258
    239 Tonalide 1850 C18H26O 258
    240 1-Nonadecene 1875 C19H38 266
    241 Nonadecane 1900 C19H40 268
    242 Falcarinol 2028 C17H24O 244
    243 Trichocoleine 1875 C14H18O4 250
    244 Ambrettolide 1905 C16H28O2 252
    245 Methyl 4-Hydroxy-3-methoxy-5- 1833 C14H18O4 250
    (1,1-dimethylprop-2-enyl)-benzoate
    246 (E)-Benzyl cinnamate 2023 C16H14O2 238
    247 trans-Pinocarvyl formate 1228 C11H16O2 180
    248 Hex-5-en-1-ol 820 C6H12O 100
    249 Hex-5-en-3-ol 832 C6H12O 100
    250 1-Hexanol 837 C6H14O 102
    251 (Z)-Hex-3-en-1-ol 851 C6H12O 100
    252 (E)-Hex-3-en-1-ol 851 C6H12O 100
    253 (Z)-Hex-2-en-1-ol 861 C6H12O 100
    254 2-Heptanone 871 C7H14O 114
    255 2-Heptanol 880 C7H16O 116
    256 3-Heptanol 877 C7H16O 116
    257 n-Heptanal 882 C7H14O 114
    258 Santene 884 C9H14 122
    259 2-Methyl-1-hexanol 917 C7H16O 116
    260 Tricyclene 927 C10H16 136
    261 a-Pinene 936 C10H16 136
    262 Benzaldehyde 941 C7H6O 106
    263 a-Fenchene 941 C10H16 136
    264 Thuja-2,4(10)-diene 946 C10H14 134
    265 6-Methyl-2-heptanol 950 C8H18O 130
    266 Camphene 950 C10H16 136
    267 1-Octen-3-ol 962 C8H16O 128
    268 3-Octanone 969 C8H16O 128
    269 4-Octanol 973 C8H18O 130
    270 2-Octanol 981 C8H18O 130
    271 3-Octanol 981 C8H18O 130
    272 2-Pentylfuran 981 C9H14O 138
    273 Yomogialcohol 991 C10H18O 154
    274 3,6-Dimethyl-3-heptanol 990 C9H20O 144
    275 D 2-Carene 1000 C10H16 136
    276 a-Phellandrene 1002 C10H16 136
    277 (Z)-Hex-3-enyl acetate 1002 C8H14O2 142
    278 p-Methylanisol 1004 C8H10O 122
    279 Benzyl alcohol 1006 C7H8O 108
    280 D 3-Carene 1010 C10H16 136
    281 Phenylacetaldehyde 1012 C8H8O 120
    282 m-Cymene 1013 C10H14 134
    283 p-Cymene 1015 C10H14 134
    284 Salicylaldehyde 1020 C7H6O2 122
    285 Limonene 1025 C10H16 136
    286 1,8-Cineol 1024 C10H18O 154
    287 (Z)-b-Ocimene 1029 C10H16 136
    288 (E)-2-Octenal 1034 C8H14O 126
    289 5,5-Dimethylbut-3-enolide 916 C6H8O2 112
    290 Methyl 3-methylfuroate 1038 C7H8O3 140
    291 (E)-b-Ocimene 1041 C10H16 136
    292 Oct-3-en-1-ol (Isomer 1) 1044 C8H16O 128
    293 Artemisia ketone 1044 C10H16O 152
    294 cis-Dihydroroseoxide 1047 C10H20O 156
    295 d-Terpineol 1155 C10H16O 152
    296 g-Terpinene 1051 C10H16 136
    297 trans-Sabinene hydrate 1053 C10H18O 154
    298 Dihydromyrcenol 1058 C10H20O 156
    299 Non-1-en-3-ol 1058 C9H18O 142
    300 trans-Linalooloxide (furanoid) 1058 C10H20O2 172
    301 p-Mentha-3,8-diene 1059 C10H16 136
    302 Benzyl formate 1060 C8H8O2 136
    303 m-Cresol 1061 C7H8O 108
    304 p-Cresol 1062 C7H8O 108
    305 1-Octanol 1063 C8H18O 130
    306 Fenchone 1069 C10H16O 152
    307 o-Guiacol 1072 C7H8O2 124
    308 Methyl benzoate 1072 C8H8O2 136
    309 cis-Linalool oxide (furanoid) 1072 C10H18O2 170
    310 Artemisia alcohol 1073 C10H18O 154
    311 Dehydrolinalool 1073 C10H16O 152
    312 trans-Dihydroroseoxide 1075 C10H20O 156
    313 4-Nonanol 1076 C9H20O 144
    314 Terpinolene 1082 C10H16 136
    315 cis-Sabinene hydrate 1082 C10H18O 154
    316 2-Nonanol 1085 C9H20O 144
    317 Linalool 1086 C10H18O 154
    318 Photocitral B 1086 C10H16O 152
    319 a-Thujone 1089 C10H16O 152
    320 2,2′,5,6-Tetramethylcyclohexanone 1092 C10H18O 154
    (Isomer 1)
    321 1-Oct-3-enyl acetate 1093 C10H18O2 170
    322 4,8-Dimethyl-1,3,7-nonatriene 1096 C11H18 150
    (Isomer 1)
    323 a-Pinene epoxide (Isomer 1) 1096 C10H16O 152
    324 a-Fenchol 1099 C10H18O 154
    325 cis-Rose oxide 1100 C10H18O 154
    326 Isochrysanthenone 1086 C10H14O 150
    327 b-Thujone 1103 C10H16O 152
    328 a-Campholenal 1105 C10H16O 152
    329 2,2′,5,6-Tetramethylcyclohexanone 1106 C10H18O 154
    (Isomer 2)
    330 2-Methyl-5-propionylfuran 1108 C8H10O2 138
    331 cis-p-Menth-2-en-1-ol 1108 C10H18O 154
    332 (Z)-Ocimenoxide 1115 C10H16O 152
    333 4,8-Dimethylnona-1,3,7-triene 1115 C11H18 150
    (Isomer 2)
    334 a-Pinene epoxide (Isomer 2) 1116 C10H16O 152
    335 trans-Rose oxide 1116 C10H18O 154
    336 Dihydrolinalool 1118 C10H20O 156
    337 Ipsdienol 1123 C10H16O 152
    338 Camphor 1123 C10H16O 152
    339 trans-p-Menth-2-en-1-ol 1123 C10H18O 154
    340 (E)-Ocimenoxide 1125 C10H16O 152
    341 p-Mentha-1,5-diene-8-ol 1127 C10H16O 152
    342 trans-Pinocarveol 1126 C10H16O 152
    343 cis-Limonene oxide 1126 C10H16O 152
    344 Photocitral A 1127 C10H16O 152
    345 o-Cymenene 1076 C10H12 132
    346 (E)-Tagetone 1128 C10H16O 152
    347 (Z)-Tagetone 1136 C10H16O 152
    348 trans-Limonene oxide 1130 C10H16O 152
    349 Isopulegol 1132 C10H18O 154
    350 1,3-Dimethoxybenzene 1136 C8H10O2 138
    351 Menthone 1136 C10H18O 154
    352 Pinocarvone 1137 C10H14O 150
    353 b-Terpineol 1137 C10H18O 154
    354 (E)-Non-2-enal 1139 C9H16O 140
    355 Isoneral 1140 C10H16O 152
    356 cis-b-Terpineol 1141 C10H18O 154
    357 Isoborneol 1142 C10H18O 154
    358 Karahanaenone 1142 C10H16O 152
    359 cis- or trans-Linalool oxide 1144 C10H18O2 170
    (pyranoid)
    360 Isomenthone 1146 C10H18O 154
    361 cis-Chrysanthenol 1147 C10H16O 152
    362 2-Hydroxyethyl-4-methylbenzene 1147 C9H12O 136
    363 4-Isopropylcyclohexanone 1148 C9H16O 140
    364 cis- or trans-Linalool oxide 1148 C10H18O2 170
    (pyranoid)
    365 cis-Isopulegone 1148 C10H16O 152
    366 Methyl phenylacetate 1148 C9H10O2 150
    367 cis-Thujol 1149 C10H18O 154
    368 b-Pinene epoxide 1149 C10H16O 152
    369 Ethyl benzoate 1150 C9H10O2 150
    370 Borneol 1150 C10H18O 154
    371 Lavandulol 1150 C10H18O 154
    372 Umbellulone 1152 C10H14O 150
    373 trans-Chrysanthemol 1153 C10H18O 154
    374 Neomenthol 1156 C10H20O 156
    375 Viridene 1159 C10H12O 148
    376 Isogeranial 1156 C10H16O 152
    377 cis-Chrysanthemol 1157 C10H18O 154
    378 Benzoic acid 1160 C7H6O2 122
    379 3-Thujene-10-al 1158 C10H14O 150
    380 Cryptone 1160 C9H14O 138
    381 Terpinen-4-ol 1164 C10H18O 154
    382 b-Pinene epoxide (Isomer) 1170 C10H16O 152
    383 Nona-2,4-dienal 1170 C9H14O 138
    384 Methyl salicylate 1171 C8H8O3 152
    385 2-Methyl-2-borneol 1175 C11H20O 168
    386 2-Allylphenol 1174 C9H10O 134
    387 Thujopsa-3-one 1645 C15H24O 220
    388 7-Hydroxyhotrienol 1177 C10H18O2 170
    389 Myrtenol 1178 C10H16O 152
    390 cis-Piperitol 1181 C10H18O 154
    391 Safranal 1182 C10H14O 150
    392 Estragol (Methylchavicol) 1175 C10H12O 148
    393 2-Decanol 1188 C10H22O 158
    394 g-Terpineol 1188 C10H18O 154
    395 (E,E)-Nona-2,4-dienal 1188 C9H14O 138
    396 Methyl a-cyclogeranate 1190 C11H18O2 182
    397 trans-Piperitol 1193 C10H18O 154
    398 Chrysanthenone 1110 C10H14O 150
    399 Fenchyl acetate 1205 C12H20O2 196
    400 Benzylacetone 1207 C10H12O 148
    401 2-epi-Thujopsa-3-one 1634 C15H24O 220
    402 Carvotanacetone 1220 C10H16O 152
    403 Menthol 1172 C10H20O 156
    404 Isomenthol 1176 C10H20O 156
    405 a-Terpinyl acetate 1335 C10H16 136
    406 Octyl acetate 1188 C10H20O2 172
    407 Dillether 1170 C10H16O 152
    408 (E)-Ethyl cinnamate 1439 C11H12O2 176
    409 b-Ionone 1468 C13H20O 192
    410 Piperonal 1294 C8H6O3 150
    411 Vanilline 1355 C8H8O3 152
    412 Coumarin 1392 C9H6O2 146
    413 (Z)-2-Hexylcinnamic aldehyde 1725 C15H20O 216
    414 1-Phenylethyl acetate 1166 C10H12O2 164
    415 (Z)-2-Pentylcinnamaldehyde 1632 C14H18O 202
    416 Benzyl salicylate 1847 C14H12O3 228
    417 Menthofuran 1150 C10H14O 150
    418 a-Campholenol 1190 C10H18O 154
    419 Methyl jasmonate 1611 C13H20O3 224
    420 Isophytol 1949 C20H40O 296
    421 Phytol 2114 C20H40O 296
    422 (E)-Anyl 2-methylbutyrate 1651 C14H18O2 218
    423 (E)-4-4Propenylphenol tiglate 1765 C14H16O2 216
    424 trans-Epoxypseudoisoeugenyl-2- 1871 C15H20O4 264
    methylbutyrate
    425 (E)-Pseudoisoeugenyl tiglate 1895 C15H18O3 246
    426 trans-Epoxypseudoisoeugenol tiglate 1942 C15H18O4 262
    427 Dictyotene 1155 C11H18 150
    428 Desmarestene 1168 C11H14 146
    429 Dictyopterene A 1099 C11H18 150
    430 Ectocarpene 1136 C11H16 148
    431 (E)-Ectocarpene 1147 C11H16 148
    432 cis-Hormosirene 1152 C11H16 148
    433 trans-Hormosirene 1160 C11H16 148
    434 (Z)-Multifidene 1040 C11H16 148
    435 (E)-Multifidene 1047 C11H16 148
    436 (E)-Aucantene 1062 C11H16 148
    437 (E)-Aucantene 1077 C11H16 148
    438 cis-Dihydromultifidene 1052 C11H18 150
    439 trans-Dihydromultifidene 1058 C11H18 150
    440 Neothujol 1136 C10H16O 152
    441 (Z)-Methyl cinnamate 1270 C10H10O2 162
    442 Isothujol 1121 C10H16O 152
    443 Neoisothujol 1132 C10H16O 152
    444 Citronellal 1129 C10H18O 154
    445 2-Methyl-2-pentanol 944 C6H14O 102
    446 6-Acetoxy-p-mentha-1(7),8-diene 1312 C12H18O2 194
    (Isomer 1)
    447 n-Nonanal 1076 C9H18O 142
    448 5,7-Dimethylocta-1,6-diene 911 C10H18 138
    449 Dec-9-en-1-ol 1240 C10H20O 156
    450 Elsholtzia ketone 1175 C10H14O2 166
    451 a-Dehydroelsholtzia ketone 1188 C10H12O2 164
    452 Dehydroelsholtzia ketone 1277 C10H12O2 164
    453 4-Methyl-3-heptanol 956 C8H18O 130
    454 6-Methylhept-5-en-2-ol (Sulcatol) 981 C8H16O 128
    455 b-Helmiscapene 1446 C15H24 204
    456 2,2-Dimethyl-4-oxocyclohexane-1- 1132 C9H14O2 154
    carbaldehyde
    457 Menth-1-en-9-ol 1283 C10H18O 154
    458 cis-Dihydrocarvone 1172 C10H16O 152
    459 trans-Dihydrocarvone 1177 C10H16O 152
    460 Limonen-10-ol 1272 C10H16O 152
    461 Tuberolactone 1437 C10H14O2 166
    462 trans-Carveol 1200 C10H16O 152
    463 Dihydrocarveol (Isomer 1) 1176 C10H18O 154
    464 Dihydrocarveol (Isomer 2) 1193 C10H18O 154
    465 Dihydrocarveol (Isomer 3) 1205 C10H18O 154
    466 cis-Carveol 1210 C10H16O 152
    467 4-Methoxyphenylacetone 1343 C10H12O2 164
    468 4-Methoxypropiophenone 1415 C10H12O2 164
    469 Grandisol 1200 C10H18O 154
    470 Hotrienol 1083 C10H16O 152
    471 Isopinocampheol 1168 C10H16O 152
    472 (E)-Pseudoisoeugenyl-2-methyl 1823 C15H20O3 248
    butyrate
    473 Falcarinone 1990 C17H22O 242
    474 Ethyl salicylate 1245 C9H10O3 166
    475 1,2-Dihydro-1,1,6-trimethyl- 1339 C13H16 172
    naphthalene
    476 g-Hexanolide 1006 C6H10O2 114
    477 g-Heptanolide 1103 C7H12O2 128
    478 g-Octanolide 1208 C8H14O2 142
    479 g-Nonanolide 1318 C9H16O2 156
    480 g-Decanolide 1433 C10H18O2 170
    481 g-Undecanolide 1547 C11H20O2 184
    482 g-Dodecanolide 1656 C12H22O2 198
    483 g-Tetradecanolide 1866 C14H26O2 226
    484 d-Nonanolide 1348 C9H16O2 156
    485 d-Octanolide 1240 C8H14O2 142
    486 d-Heptanolide 1156 C7H12O2 128
    487 d-Decanolide 1461 C10H18O2 170
    488 (E)-a-Damascone 1375 C13H20O 192
    489 4-Methyl-3-heptanone 918 C8H16O 128
    490 a-Ionone 1409 C13H20O 192
    491 p-Methylacetophenone 1156 C9H10O 134
    492 b-Cyclocitral 1195 C10H16O 152
    493 cis-a-Irone 1520 C14H22O 206
    494 cis-g-Irone 1525 C14H22O 206
    495 Dodecanal 1389 C12H24O 184
    496 Methyl linolenate 2102 C19H32O2 292
    497 Geranylacetone 1430 C13H22O 194
    498 trans-Isolimonene 975 C10H16 136
    499 cis-Myrtanol 1238 C10H18O 154
    500 n-Octanal 981 C8H16O 128
    501 p-Menth-1-ene 1017 C15H18 198
    502 (E)-Jasmone 1356 C11H16O 164
    503 trans-Myrtanol 1240 C10H18O 154
    504 allo-Ocimene 1113 C10H16 136
    505 (4E,6Z)-allo-Ocimene 1126 C10H16 136
    506 Dodecanol 1472 C12H26O 186
    507 6-Acetoxy-p-menta-1,8-diene 1341 C12H18O2 194
    508 b-Citronellene 943 C15H18 198
    509 n-Nonanol 1149 C9H20O 144
    510 trans-Sabinol 1120 C10H16O 152
    511 3,5-Dimethoxytoluene 1231 C9H12O2 152
    512 Phantolide 1712 C17H24O 244
    513 Perilla alcohol 1280 C10H16O 152
    514 b-Phellandrene 1023 C10H16 136
    515 b-Phenylethanol 1085 C8H10O 122
    516 Citronellol 1213 C10H20O 156
    517 Methyleugenol 1369 C11H14O2 178
    518 2-Nonanone 1074 C9H18O 142
    519 2-Decanone 1176 C10H20O 156
    520 2-Dodecanone 1381 C12H24O 184
    521 4-Isopropylcyclohexanol (Isomer 2) 1130 C9H18O 142
    522 Moskachane B 1794 C13H16O3 220
    523 Moskachane D 2001 C15H20O3 248
    524 cis-Verbenol 1132 C10H16O 152
    525 (Z)-Salvene 849 C9H16 124
    526 (E)-Salvene 859 C9H16 124
    527 Santolinatriene 909 C10H16 136
    528 a-Thujene 932 C10H16 136
    529 Sabinene 973 C10H16 136
    530 a-Terpinene 1013 C10H16 136
    531 trans-Verbenol 1136 C10H14O 150
    532 Verbenone 1183 C10H14O 150
    533 Z-Cinnamaldehyde 1185 C9H8O 132
    534 3-Phenylpropanol 1201 C9H12O 136
    535 (E)-Cinnamyl alcohol 1275 C9H10O 134
    536 b-Irone 1566 C14H22O 206
    537 Benzyl acetate 1134 C9H10O2 150
    538 Indole 1257 C8H7N 117
    539 d-Jasmolactone 1450 C10H16O2 168
    540 N-Acetyl methyl anthranilate 1565 C10H11O3N 193
    541 Benzyl benzoate 1730 C14H12O2 212
    542 6-Methylhept-5-en-2-one 978 C8H14O 126
    543 Rosefuran 1091 C10H14O 150
    544 Rosefuran epoxide 1161 C10H14O2 166
    545 b-Pinene 978 C10H16 136
    546 Myrcene 987 C10H16 136
    547 Oct-3-en-1-ol (Isomer 2) 1049 C8H16O 128
    548 6-Acetoxy-p-mentha-1(7),8-diene 1343 C12H18O2 194
    (Isomer 2)
    549 (E)-4-Propenylphenol angelate 1751 C14H16O2 216
    550 cis-Epoxypseudoisoeugenyl-2- 1870 C15H20O4 264
    methyl butyrate
    551 Myrtenal 1172 C10H14O 150
    552 (E)-Ocimenone 1219 C10H14O 150
    553 (Z)-Ocimenone 1209 C10H14O 150
    554 Isomenthyl acetate 1298 C12H22O2 198
    555 Thymoquinone 1215 C10H12O2 164
    556 Cymen-9-ol 1157 C10H14O 150
    557 8,9-Dehydrothymol 1190 C10H12O 148
    558 (Z)-Methyl p-hydroxycinnamate 1603 C10H10O3 178
    559 b-Thujaplicine 1449 C10H12O2 164
    560 n-Undecane 1100 C11H24 156
    561 n-Nonane 906 C9H20 128
    562 Pinocamphone 1139 C10H16O 152
    563 Isopinocamphone 1151 C10H16O 152
    564 Methyl 2-methylbutyrate 954 C6H12O2 116
    565 6-Methylhept-5-enal 985 C8H14O 126
    566 Furomyrcenol 1256 C10H14O2 166
    567 a-Ionone epoxide (Isomer 1) 1516 C13H20O2 208
    568 o-Cresol 1037 C7H8O 108
    569 (E)-2-Hexenal 832 C6H10O 98
    570 Ethyl 2-methylbutyrate 843 C7H14O2 130
    571 p-Mentha-2,4(8)-diene 1077 C10H16 136
    572 p-Mentha-1,3,8-triene 1101 C10H16 136
    573 Neroloxide 1137 C10H16O 152
    574 Neoisopulegol 1150 C10H18O 154
    575 (E,E)-Nona-3,6-dien-1-ol 1145 C9H16O 140
    576 n-Pentylbenzene 1150 C11H16 148
    577 (Z)-Ethyl oct-5-enoate 1174 C10H18O2 170
    578 a-Terpineol 1176 C10H18O 154
    579 2a-Hydroxy-1,8-cineol 1196 C10H18O2 170
    580 cis-Pulegol 1215 C10H18O 154
    581 3b-Hydroxy-1,8-cineol 1229 C10H18O2 170
    582 Linalyl acetate 1239 C12H20O2 196
    583 Isopiperitenone 1240 C10H14O 150
    584 Piperitenone 1318 C10H14O 150
    585 Piperitenone oxide 1335 C10H14O2 166
    586 Geranyl acetate 1362 C12H20O2 196
    587 2-Methylbutyl benzoate 1419 C12H16O2 192
    588 Myristicine 1489 C11H12O3 192
    589 Acetophenone 1036 C8H8O 120
    590 Dihydrotagetone 1047 C10H18O 154
    591 p-Cymenene 1075 C10H12 132
    592 Piperiton epoxid 1232 C10H16O2 168
    593 Nepetalacton (Isomer 2) 1360 C10H14O2 166
    594 3,4-Dimethyl-5-pentyl-5H-furan-2- 1481 C11H18O2 182
    one
    595 Methyl p-methoxybenzoate 1338 C9H10O3 166
    596 (E)-o-Methoxycinnamyl alcohol 1488 C10H12O2 164
    597 (E)-m-Methoxycinnamyl alcohol 1511 C10H12O2 164
    598 (E)-p-Methoxycinnamyl alcohol 1523 C10H12O2 164
    599 Perillene 1090 C10H14O 150
    600 Methyl anthranilate 1308 C8H9O2N 151
    601 1-(3-Methoxyphenyl)-2- 1735 C15H16O 212
    phenylethane
    602 1-Phenyl-2-(3,5-dimethoxyphenyl)- 1962 C16H18O2 242
    ethane
    603 1-(3-Methoxyphenyl)-2-(4- 1988 C16H18O2 242
    methoxyphenyl)-ethane
    604 Neryl isobutyrate 1468 C14H24O2 224
    605 Zingiberenol 1596 C14H24O 208
    606 Encecalin 1813 C14H16O3 232
    607 Ethyl p-methoxybenzoate 1415 C10H12O3 180
    608 Albanone 1389 C12H18O 178
    609 7,10-Anhydro-11,12- 1449 C15H24O 220
    dihydrochiloscypholone
    610 1(11)-Africanen-8-ol 1486 C15H24O 220
    611 Atractylone 1497 C15H20O 216
    612 Conocephalenol 1497 C15H26O 222
    613 Cubebol 1514 C15H26O 222
    614 Photosantalol 1511 C15H24O 220
    615 Cyperene epoxide 1524 C15H24O 220
    616 Isoafricanol 1529 C15H26O 222
    617 cis-Cadina-4,6-dien-11-ol 1531 C15H24O 220
    618 Elema-1,3-dien-7-ol 1531 C15H24O 220
    619 Tamariscol 1535 C15H26O 222
    620 Pacifigorgiol 1539 C15H26O 222
    621 (E,E)-Methyl 10-oxofarnesoate 1896 C16H26O3 266
    622 b-Caryophyllene oxide 1546 C15H24O 220
    623 Africanone 1547 C15H22O 218
    624 1,8-Oxidocadin-4-ene 1551 C15H24O 220
    625 4bH,5aH-cis-Eudesm-6-en-11-ol 1555 C15H26O 222
    626 Dactylol 1556 C15H26O 222
    627 cis-Sesquisabinenhydrate 1558 C15H26O 222
    628 11,12-Dihydrochiloscyphone 1558 C15H24O 220
    629 Aromadendran-5-ol 1562 C15H26O 222
    630 Oxidohimachalene 1557 C15H22O 218
    631 (+)-Marsupellol 1564 C15H24O 220
    632 b-Himachalol 1638 C15H26O 222
    633 Maaliol 1565 C15H26O 222
    634 Deoxopinguisone 1563 C15H22O 218
    635 Palustrol 1569 C15H26O 222
    636 4a-Hydroxygermacra-1(10),5-diene 1571 C15H26O 222
    637 Spathulenol 1572 C15H24O 220
    638 4-Dehydroviridiflorol 1572 C15H24O 220
    639 Caryophyllene oxide 1578 C15H24O 220
    640 7-Acetoxyelema-1,3,8-triene 1584 C17H26O2 262
    641 Globulol 1589 C15H26O 222
    642 Cubeban-11-ol 1591 C15H26O 222
    643 Salvial-4(14)-en-1-one 1592 C15H24O 220
    644 Bisabola-2,10-diene 1,9-oxide 1592 C15H24O 220
    645 b-Oplopenone 1595 C15H24O 220
    646 Longiborneol 1597 C15H26O 222
    647 Rosifoliol 1599 C15H26O 222
    648 Ledol 1600 C15H26O 222
    649 2-Methyl-1-(octahydro-7,7a- 1601 C15H26O 222
    dimethyl-1H-inden-1-yl)-propan-1-
    one
    650 Eudesm-4-en-7-ol 1604 C15H26O 222
    651 Rearrangement product from 1608 C15H22O 218
    Grimaldone
    652 Maalian-5-ol 1607 C15H26O 222
    653 10-epi-g-Eudesmol 1609 C15H26O 222
    654 ar-Curcumen-7-ol 1610 C15H22O 218
    655 Amorpha-4,7-dien-11-ol 1610 C15H24O 220
    656 5-Guaiene-11-ol 1619 C15H26O 222
    657 g-Eudesmol 1618 C15H26O 222
    658 Alismol 1619 C15H24O 220
    659 Gymnomitrone 1620 C15H22O 218
    660 Isospathulenol 1625 C15H24O 220
    661 Isogymnomitrol 1625 C15H24O 220
    662 Furanoeudesm-1,3-diene 1630 C15H18O 214
    663 Amorpha-4-en-7-ol 1629 C15H26O 222
    664 Eudesm-3,11-dien-5-ol 1632 C15H24O 220
    665 Hinesol 1632 C15H26O 222
    666 T-Muurolol 1633 C15H26O 222
    667 (E,E)-Germacradiene-11-ol 1633 C15H26O 222
    668 T-Cadinol 1633 C15H26O 222
    669 Gymnomitr-3(15)-en-4-one 1635 C15H22O 218
    670 1(10)-Spirovetivene-7b-ol 1636 C15H26O 222
    671 Muurola-3,7(11)-dien-1-ol 1637 C15H24O 220
    672 6-Himachalen-9b-ol 1638 C15H26O 222
    673 Gymnomitran-4-one 1639 C15H24O 220
    674 b-Eudesmol 1641 C15H26O 222
    675 Furanoeremophilene 1642 C15H22O 218
    676 2-Himachalen-7b-ol 1642 C15H26O 222
    677 a-Cadinol 1643 C15H26O 222
    678 Eudesm-4(15)-en-7-ol 1643 C15H24O 220
    679 2-Methyl-1-(octahydro-7,7a- 1645 C15H28O 224
    dimethyl-1H-inden-1-yl)-propan-1-
    ol
    680 Eudesm-11-en-4a-ol 1649 C15H26O 222
    681 1(10)-Valencen-7b-ol 1646 C15H26O 222
    682 Valerianol 1647 C15H26O 222
    683 Eudesm-3-en-7-ol 1650 C15H26O 222
    684 10-epi-trans-Dracunculifoliol 1591 C15H26O 222
    685 7-epi-a-Eudesmol 1653 C15H26O 222
    686 Acorenol B 1654 C15H26O 222
    687 Bisabolol oxide B 1654 C15H26O2 238
    688 Aromadendran-12-ol 1654 C15H24O 220
    689 Grimaldone 1656 C15H22O 218
    690 Gymnomitrol 1657 C15H24O 220
    691 Eudesm-4(15)-en-6-ol 1656 C15H26O 222
    692 Saccogynol 1660 C15H22O 218
    693 Valeranone 1664 C15H26O 222
    694 4-epi-Acorenone 1664 C15H24O 220
    695 Gymnomitr-3(15)-en-4a-ol 1665 C15H24O 220
    696 Acorenol 1667 C15H26O 222
    697 epi-Cyclosantalal 1668 C15H24O 220
    698 (Z)-g-Atlantone 1669 C15H22O 218
    699 a-Alasken-6-ol 1674 C15H24O 220
    700 Bisabolone oxide A 1675 C15H24O2 236
    701 Amorpha-4,7(11)-dien-8-one 1679 C15H22O 218
    702 Amorpha-4,9-dien-2-ol 1679 C15H24O 220
    703 Amorpha-4,9-dien-14-al 1685 C15H22O 218
    704 Eudesm-3-en-6-ol 1679 C15H26O 222
    705 Khusiol 1680 C15H26O 222
    706 (E)-g-Atlantone 1681 C15H22O 218
    707 Acorenone 1681 C15H24O 220
    708 Cadina-1(10),4-dien-8a-ol 1682 C15H24O 220
    709 Bicyclogermacren-14-al 1684 C15H22O 218
    710 Cyperotundone 1684 C15H22O 218
    711 (Z)-a-Atlantone 1689 C15H22O 218
    712 Lanceol oxide 1695 C15H24O 220
    713 Farnesol (Isomer 1) 1694 C15H26O 222
    714 6a-Hydroxygermacra-1(10),4-diene 1687 C15H26O 222
    715 Acora-7(11),9-dien-2-one 1706 C15H22O 218
    716 Valerenal 1706 C15H22O 218
    717 a-Herbertenol 1711 C15H22O 218
    718 Dihydrochiloscypholone 1711 C15H26O2 238
    719 Italicen-4-one 1717 C15H22O 218
    720 Farnesol (Isomer 2) 1718 C15H26O 222
    721 10-epi-1,8-Oxidocadina-4-ene 1539 C15H24O 220
    722 Neopetasone 1733 C15H22O 218
    723 7,14-Anhydroamorpha-4,9-diene 1733 C15H22O 218
    724 Lepidozenal 1744 C15H22O 218
    725 7-Acetoxyelema-1,3-dien-8-ol 1793 C17H28O3 280
    726 Naviculol 1734 C15H26O 222
    727 Bisabolol oxide A 1740 C15H26O2 238
    728 a-Cyperone 1741 C15H22O 218
    729 Cyclocolorenone 1745 C15H22O 218
    730 Gymnomitrol acetate 1751 C17H26O2 262
    731 b-Herbertenol 1751 C15H22O 218
    732 (E)-a-Atlantone 1754 C15H22O 218
    733 (Z)-Lanceol 1755 C15H24O 220
    734 Cuparophenol 1763 C15H22O 218
    735 Cedryl acetate 1764 C17H28O2 264
    736 14-Oxocalamenene 1768 C15H20O 216
    737 Isovalencenol 1779 C15H24O 220
    738 Drimenol 1750 C15H26O 222
    739 cis-5-Hydroxycalamenene 1790 C15H22O 218
    740 Khusienol acetate 1789 C17H26O2 262
    741 Fukinanolide 1798 C15H22O2 234
    742 Bisabola-2,7(Z),10(Z)-triene-13-ol 1806 C15H24O 220
    743 Cyperadione 1820 C15H24O2 236
    744 cis-Spiroether 1850 C13H12O2 200
    745 trans-Spiroether 1853 C13H12O2 200
    746 trans-4,8a-Dimethyl-4a,5- 1350 C12H20O 180
    epoxydecaline
    747 Peculiaroxide 1416 C15H26O 222
    748 Furanoelemene 1485 C15H20O 216
    749 Guaioxide 1487 C15H26O 222
    750 Elemol 1541 C15H26O 222
    751 Lemnalol 1579 C15H24O 220
    752 Fokienol 1582 C15H24O 220
    753 Thujopsane-2b-ol 1593 C15H26O 222
    754 a-Alasken-8-ol 1600 C15H24O 220
    755 6-epi-Cubenol 1602 C15H26O 222
    756 Widdrol 1601 C15H26O 222
    757 Marsupellone 1604 C15H22O 218
    758 Axinyssene 1860 C20H32 272
    759 Selina-1,3,7(11)-trien-8-one 1616 C15H20O 216
    760 Myliol 1617 C15H22O 218
    761 a-Acorenol 1623 C15H26O 222
    762 Furanogermacrene 1624 C15H20O 216
    763 Acora-3,7(11)-dien-6-ol 1626 C15H24O 220
    764 b-Acorenol 1626 C15H26O 222
    765 a-Alaskene-8-ol 1632 C15H24O 220
    766 Microbiotol 1632 C15H26O 222
    767 Isopinguisanine 1638 C15H20O2 232
    768 Gymnomitr-3(15)-en-4b-ol 1653 C15H24O 220
    769 a-Eudesmol 1653 C15H26O 222
    770 Isorotundenol 1659 C15H26O 222
    771 Bulnesol 1665 C15H26O 222
    772 Bicyclohumulenone 1668 C15H24O 220
    773 Selina-4(15),11-dien-8-ol 1670 C15H24O 220
    774 Smyrnicordifuran 1673 C15H18O2 230
    775 b-Sinensal 1675 C15H22O 218
    776 Isocyperol 1676 C15H24O 220
    777 a-Cuparenone 1681 C15H20O 216
    778 Cyperol 1681 C15H24O 220
    779 Gymnomitr-3-en-15-ol 1688 C15H24O 220
    780 Pinguisanine 1706 C15H20O2 232
    781 Acora-3,7(11)-dien-8-one 1709 C15H22O 218
    782 Vetiselinol 1709 C15H24O 220
    783 10,11-Dihydro-a-cuparenone 1712 C15H22O 218
    784 Oxidoselina-1,3,7(11)-trien-8-one 1725 C15H20O2 232
    785 a-Sinensal 1726 C15H22O 218
    786 Plagiochilide 1729 C15H20O2 232
    787 (E,E)-Methyl 10,11-epoxyfarnesoate 1875 C16H26O3 266
    788 Eudesma-3,11-dien-2-one 1776 C15H22O 218
    789 Zizaenic acid 1791 C15H22O2 234
    790 Acutifolene B 1806 C15H20O3 248
    791 a-Vetivone 1821 C15H22O 218
    792 (E,E)-Farnesylacetate 1822 C17H28O2 264
    793 Acutifolene A 1833 C16H22O3 262
    794 Furanoeremophilone 1855 C15H20O2 232
    795 2-Acetoxyfuranoelemene 1876 C17H22O3 274
    796 Guaia-3,10(14)-dien-6,12-olide 1938 C15H20O2 232
    797 Guaia-3,7(11),10(14)-trien-6,12- 1950 C15H18O2 230
    olide
    798 1b-Acetoxyfurano-4(15)-eudesmene 1964 C17H22O3 274
    799 1b-Acetoxyfurano-3-eudesmene 1978 C17H22O3 274
    800 Maalioxide 1508 C15H26O 222
    801 Kessane 1533 C15H26O 222
    802 Humulene epoxide 3 1626 C15H24O 220
    803 8-Hydroxybicyclogermacrene 1661 C15H24O 220
    804 Lactarovioline 2068 C15H14O 210
    805 5-epi-Pinguisenol 1764 C15H26O 222
    806 b-Santalol acetate 1800 C17H26O2 262
    807 Bisacumol (Isomer 1) 1596 C15H22O 218
    808 Bisacumol (Isomer 2) 1619 C15H22O 218
    809 Bisabola-1,3(15),10-trien-9-ol 1666 C15H24O 220
    (Isomer 1)
    810 Bisabola-1,3(15),10-trien-9-ol 1678 C15H24O 220
    (Isomer 2)
    811 trans-Sesquisabinen hydrate 1564 C15H26O 222
    812 1bH-Presilphiperfolane-9a-ol 1510 C15H26O 222
    813 1aH-Presilphiperfolan-9b-ol 1499 C15H26O 222
    814 Presilphiperfolane-9a-ol 1519 C15H26O 222
    815 ar-Curcumen-15-al 1681 C15H20O 216
    816 Sesquicineol 1507 C15H26O 222
    817 Italicen-13-al 1671 C15H22O 218
    818 a-Copaen-8-ol 1551 C15H24O 220
    819 Khusimol 1720 C15H24O 220
    820 Zizanol 1656 C15H24O 220
    821 Oxidocadalene 1644 C15H18O 214
    822 Eremoligenol 1614 C15H26O 222
    823 Isohumbertiol D (Isomer 2) 1519 C15H24O 220
    824 Isohumbertiol D (Isomer 1) 1490 C15H24O 220
    825 Brachylaenalone B 1824 C15H20O2 232
    826 Khusien-12-al 1580 C15H22O 218
    827 Eudesma-4(15),7(11)-dien-8-one 1713 C15H22O 218
    828 Elemenone 1589 C15H22O 218
    829 b-Cedrene epoxide 1610 C15H24O 220
    830 b-Panasinsen-5a-ol 1621 C15H24O 220
    831 Eudesm-7(11)-en-4a-ol 1676 C15H26O 222
    832 5,8-Cyclocaryophyllan-4-ol 1514 C15H26O 222
    833 Khusol 1769 C15H24O 220
    834 cis-10-Hydroxycalamenene 1643 C15H22O 218
    835 trans-10-Hydroxycalamenene 1635 C15H22O 218
    836 Bryopterine A 1735 C16H20O3 260
    837 Isoitalicene epoxide 1501 C15H24O 220
    838 Italicene epoxide 1535 C15H24O 220
    839 a-Agarofuran 1537 C15H24O 220
    840 Longipin-3-en-10-ol 1560 C15H24O 220
    841 Dihydrosesquicineol 1467 C15H28O 224
    842 Dehydrosesquicineol 1466 C15H24O 220
    843 Longicamphenilone 1549 C14H22O 206
    844 Longicamphenilol 1578 C14H24O 208
    845 Isobutyl angelate 1027 C9H16O2 156
    846 Isoacorone 1774 C15H24O2 236
    847 Dehydrosesquicineyl-12-ol 1707 C15H24O2 236
    848 Dihydrobryopterine A 1763 C16H22O3 262
    849 (E)-Nuciferal 1705 C15H20O 216
    850 (Z)-Nuciferal 1695 C15H20O 216
    851 Pinguisanene 1544 C15H20O 216
    852 (E)-Methyl 10-hydroxy-3,7,11- 1930 C16H26O3 266
    trimethyldodeca-2,6,11-trienoate
    853 Dihydroagarofuran 1500 C15H26O 222
    854 Isolongifolol 1717 C15H26O 222
    855 (Z)-Nerolidol 1522 C15H26O 222
    856 (E)-Nerolidol 1553 C15H26O 222
    857 a-Cedrene oxide 1571 C15H24O 220
    858 Caryolan-1-ol 1567 C15H26O 222
    859 Thujopsan-2a-ol 1584 C15H26O 222
    860 Curcerenone 1588 C15H18O2 230
    861 a-Guaiol 1593 C15H26O 222
    862 Viridiflorol 1592 C15H26O 222
    863 Epicurcerenone 1593 C15H18O2 230
    864 Carotol 1594 C15H26O 222
    865 Cedrol 1603 C15H26O 222
    866 12-epi-Cedrol 1620 C15H26O 222
    867 1-epi-Cubenol 1623 C15H26O 222
    868 ar-Turmerone 1643 C15H20O 216
    869 3(15)-Cedren-4-ol 1647 C15H24O 220
    870 a-Turmerone 1649 C15H22O 218
    871 Patchouli alcohol 1661 C15H26O 222
    872 (Z)-a-Santalol 1669 C14H22O 206
    873 a-Bisabolol 1673 C15H26O 222
    874 Acorenone B 1679 C15H24O 220
    875 Germacrone 1684 C15H22O 218
    876 Curcuphenol 1693 C15H22O 218
    877 2-Butylfuran 869 C8H12O 124
    878 Pinguisone 1705 C15H20O2 232
    879 (Z)-b-Santalol 1702 C15H24O 220
    880 Xanthorhizol 1732 C15H22O 218
    881 cis-2-Hydroxycalamenene 1762 C15H22O 218
    882 Furanogermenone 1770 C15H20O2 232
    883 Alantolactone 1873 C15H20O2 232
    884 Dihydroisoalantolactone 1875 C15H22O2 234
    885 Frullanolide 1900 C15H20O2 232
    886 Isoalantolactone 1912 C15H20O2 232
    887 ent-Diplophyllolide 1937 C15H20O2 232
    888 Guaia-6,9-dien-4b-ol 1565 C15H24O 220
    889 Guaia-6,10(14)-diene-4b-ol 1610 C15H24O 220
    890 Cedrenone 1722 C15H22O 218
    891 8bH-Cedran-9-one 1608 C15H24O 220
    892 Deodarone 1676 C15H24O2 236
    893 Pogostol 1647 C15H26O 222
    894 Dihydro-ar-turmerone 1570 C15H22O 218
    895 Norpatchoulenol 1551 C14H22O 206
    896 Caryophyllan-2,6-a-oxide 1412 C15H26O 222
    897 Caryophyllen-2,6-b-oxide 1422 C15H26O 222
    898 b-Atlantol (Isomer 1) 1436 C15H24O 220
    899 b-Atlantol (Isomer 2) 1443 C15H24O 220
    900 1,11-Oxidocalamenene 1474 C15H20O 216
    901 Furopelargone A 1517 C15H22O2 234
    902 Isohumbertiol B 1522 C15H24O 220
    903 Silphiperfolene-5-ol 1549 C15H24O 220
    904 b-Funebrene epoxide 1591 C15H24O 220
    905 b-Himachalene epoxide 1594 C15H24O 220
    906 Copaborneol 1595 C15H26O 222
    907 10-epi-Italicen-4-one 1615 C15H22O 218
    908 ar-Bisabolol 1619 C15H22O 218
    909 allo-Aromadendrene epoxide 1623 C15H24O 220
    910 Amorph-4-en-10a-ol 1634 C15H26O 222
    911 alio-Himachalol 1648 C15H26O 222
    912 Farnesal (Isomer 1) 1655 C15H24O 220
    913 b-Sesquiphellandrone 1677 C15H22O 218
    914 Aromadendran-14-ol 1679 C15H26O 222
    915 Farnesal (Isomer 2) 1683 C15H24O 220
    916 Farnesal (Isomer 3) 1707 C15H24O 220
    917 Longifolol 1707 C15H26O 222
    918 Sesquichamaenol 1744 C15H22O2 234
    919 (E,E)-Methyl farnesoate 1765 C16H26O2 250
    920 trans-2-Hydroxycalamenene 1753 C15H22O 218
    921 a-Santalol acetate 1756 C17H26O2 262
    922 8-Acetoxyelemol 1759 C17H26O2 262
    923 Nootkatone 1782 C15H22O 218
    924 Striatol 1550 C15H26O 222
    925 Eremophila-1(10),11-dien-9b-ol 1552 C15H24O 220
    926 Longipinanol 1559 C15H26O 222
    927 Brachyl oxide 1599 C15H24O 220
    928 Humulene epoxide 2 1602 C15H24O 220
    929 Copaen-15-ol 1661 C15H24O 220
    930 Isonaviculol 1743 C15H26O 222
    931 Cyperenal 1741 C15H22O 218
    932 g-Curcumen-15-al 1744 C15H22O 218
    933 Brachylaenalone A 1802 C15H20O2 232
    934 Muurola-4,10(14)-dien-8a-ol 1594 C15H24O 220
    935 Cadina-1(10),4-dien-8a-ol 1637 C15H24O 220
    936 Hexyl acetate 1006 C8H16O2 144
    937 Muurola-4,10(14)-dien-8b-ol 1675 C15H24O 220
    938 (Z)-Nuciferol 1695 C15H22O 218
    939 (Z)-g-Curcumen-12-ol 1701 C15H24O 220
    940 (E)-Nuciferol 1715 C15H22O 218
    941 (Z)-g-Curcumyl acetate 1767 C17H26O2 262
    942 (Z)-Nuciferyl acetate 1793 C17H24O2 260
    943 (Z)-Nuciferyl isobutyrate 1916 C19H28O2 288
    944 (Z)-g-Curcumenyl isobutyrate 1920 C19H30O2 290
    945 (Z)-Nuciferyl 2-methylbutyrate 2003 C20H30O2 302
    946 (Z)-g-Curcumyl 2-methylbutyrate 2011 C20H32O2 304
    947 Drim-8-en-7-one 1778 C15H24O 220
    948 1-Oxo-a-longipinene 1639 C15H22O 218
    949 g-Bicyclohomofarnesal 1784 C16H26O 234
    950 Geosmin 1392 C12H22O 182
    951 Muurol-4-en-6a-ol 1609 C15H26O 222
    952 Veticadine oxide 1482 C15H24O 220
    953 Cubenol 1630 C15H26O 222
    954 4-epi-Cubebol 1490 C15H26O 222
    955 Muurol-4-en-3,8-dione 1753 C15H22O2 234
    956 3-Acetoxyamorpha-4,7(11)-dien-8- 1950 C17H24O3 276
    one
    957 (E)-4,8-Dimethylnona-1,3,7-triene 1103 C11H18 150
    958 Geijerene 1139 C12H18 162
    959 Albene 1154 C12H18 162
    960 Trinoranastreptene 1197 C12H16 160
    961 1,4a-Dimethyl-1,2,3,4,4a,5,6,7- 1233 C12H20 164
    octahydro-naphthalene
    962 Pregeijerene 1288 C12H18 162
    963 (Z)-2,6,10-Trimethylundeca-2,6- 1305 C14H26 194
    diene
    964 Isocyclobazzanene 1319 C15H24 204
    965 8,9-Didehydrocycloisolongifolene 1320 C15H22 202
    966 (E)-2,6,10-Trimethylundeca-2,6- 1321 C14H26 194
    diene
    967 Cyprotene 1322 C14H24 192
    968 Presilphiperfol-1-ene 1325 C15H24 204
    969 7aH-Silphiperfol-5-ene 1329 C15H24 204
    970 Brasila-5,10-diene 1335 C15H24 204
    971 Bicycloax-4(15)-ene 1336 C15H24 204
    972 Bicycloelemene 1338 C15H24 204
    973 d-Elemene 1340 C15H24 204
    974 3,10-Dihydro-1,4-dimethylazulene 1342 C12H14 158
    975 Presilphiperfol-7-ene 1342 C15H24 204
    976 Pentalenene 1343 C15H24 204
    977 African-5-ene 1350 C15H24 204
    978 African-2(6)-ene 1350 C15H24 204
    979 Maali-1,3-diene 1347 C15H22 202
    980 Silphin-1-ene 1350 C15H24 204
    981 7bH-Silphiperfol-5-ene 1352 C15H24 204
    982 a-Cubebene 1355 C15H24 204
    983 Tamariscene 1355 C15H24 204
    984 Africa-1,5-diene 1355 C15H22 202
    985 African-1-ene 1356 C15H24 204
    986 Bicycloax-3-ene 1357 C15H24 204
    987 Silphiperfola-5,7(14)-diene 1360 C15H22 202
    988 a-Longipinene 1360 C15H24 204
    989 Clovene 1365 C15H24 204
    990 Cyperadiene 1365 C15H22 202
    991 Cyclomyltaylane 1366 C15H24 204
    992 1-epi-a-Pinguisene 1367 C15H24 204
    993 Brasila-5(10),6-diene 1370 C15H24 204
    994 Anastreptene 1373 C15H22 202
    995 Capnell-9(12)-ene 1372 C15H24 204
    996 a-Ylangene 1376 C15H24 204
    997 Isopatchoula-3,5-diene 1377 C15H22 202
    998 Cyclosativene 1378 C15H24 204
    999 Hirsutene 1378 C15H24 204
    1000 a-Copaene 1379 C15H24 204
    1001 a-Bourbonene 1378 C15H24 204
    1002 Daucene 1380 C15H24 204
    1003 Silphiperfol-6-ene 1378 C15H24 204
    1004 Bourbon-7-ene 1381 C15H24 204
    1005 a-Elemene 1381 C15H24 204
    1006 Isodauca-4,7(14)-diene 1381 C15H24 204
    1007 Isoledene 1382 C15H24 204
    1008 Protoillud-6-ene 1382 C15H24 204
    1009 Longicyclene 1382 C15H24 204
    1010 Modhephene 1383 C15H24 204
    1011 Pacifigorgia-1(9),10-diene 1384 C15H24 204
    1012 3-epi-African-5-ene 1384 C15H24 204
    1013 10-epi-Italicene 1384 C15H24 204
    1014 Asterisca-3(15),6-diene 1385 C15H24 204
    1015 a-Funebrene 1385 C15H24 204
    1016 b-Panasinsene 1385 C15H24 204
    1017 Bicycloopposit-4-ene 1386 C15H24 204
    1018 b-Bourbonene 1386 C15H24 204
    1019 Isodauca-4,6-diene 1385 C15H24 204
    1020 African-2-ene 1387 C15H24 204
    1021 7-epi-Sesquithujene 1387 C15H24 204
    1022 b-Patchoulene 1388 C15H24 204
    1023 a-Duprezianene 1388 C15H24 204
    1024 b-Elemene 1389 C15H24 204
    1025 a-Isocomene 1389 C15H24 204
    1026 1,5-di-epi-a-Bourbonene 1389 C15H24 204
    1027 b-Cubebene 1390 C15H24 204
    1028 1,5-di-epi-b-Bourbonene 1390 C15H24 204
    1029 African-3-ene 1391 C15H24 204
    1030 Bicyclo-4(15)-oppositene 1391 C15H24 204
    1031 Isolongifolene 1393 C15H24 204
    1032 Isodauca-6,9-diene 1393 C15H24 204
    1033 Sativene 1394 C15H24 204
    1034 Pacifigorgia-1,10-diene 1400 C15H24 204
    1035 Petasitene 1398 C15H24 204
    1036 Sesquithujene 1399 C15H24 204
    1037 African-3(15)-ene 1400 C15H24 204
    1038 Cyperene 1402 C15H24 204
    1039 b-Longipinene 1403 C15H24 204
    1040 7-epi-a-Cedrene 1404 C15H24 204
    1041 Helifolene 1406 C15H24 204
    1042 7-epi-Helifolene 1406 C15H24 204
    1043 Italicene 1408 C15H24 204
    1044 Isocaryophyllene 1409 C15H24 204
    1045 b-Isocomene 1411 C15H24 204
    1046 Longifolene 1411 C15H24 204
    1047 Ylanga-2,4(15)-diene 1411 C15H22 202
    1048 cis-a-Bergamotene 1411 C15H24 204
    1049 allo-Isolongifolene 1412 C15H24 204
    1050 Cycloseychellene 1413 C15H24 204
    1051 a-Gurjunene 1413 C15H24 204
    1052 a-Barbatene 1414 C15H24 204
    1053 b-Funebrene 1418 C15H24 204
    1054 b-Maaliene 1414 C15H24 204
    1055 Pacifigorgia-1(6),10-diene 1414 C15H24 204
    1056 Cascarilladiene 1416 C15H24 204
    1057 Isosativene 1416 C15H24 204
    1058 Tritomarene 1416 C15H24 204
    1059 a-Microbiotene 1414 C15H24 204
    1060 Aristolene 1423 C15H24 204
    1061 a-Cedrene 1418 C15H24 204
    1062 Pacifigorgia-2,10-diene 1422 C15H24 204
    1063 b-Ylangene 1420 C15H24 204
    1064 (Z)-b-Farnesene 1420 C15H24 204
    1065 Acora-3,5-diene 1421 C15H24 204
    1066 (E)-b-Caryophyllene 1421 C15H24 204
    1067 a-Santalene 1422 C15H24 204
    1068 Spirovetiva-1(10),6-diene 1422 C15H24 204
    1069 b-Duprezianene 1423 C15H24 204
    1070 Opposita-4(15),7-diene 1423 C15H24 204
    1071 b-Cedrene 1424 C15H24 204
    1072 Opposita-4(15),11-diene 1424 C15H24 204
    1073 Selina-3,6-diene 1424 C15H24 204
    1074 Bourbon-11-ene 1424 C15H24 204
    1075 Dauca-3,8-diene 1428 C15H24 204
    1076 Elema-1,3,7(11),8-tetraene 1428 C15H22 202
    1077 g-Elemene 1429 C15H24 204
    1078 Isobarbatene 1428 C15H24 204
    1079 g-Maaliene 1428 C15H24 204
    1080 Aristola-1(10),8-diene 1429 C15H22 202
    1081 Chenopodene 1430 C15H24 204
    1082 b-Copaene 1430 C15H24 204
    1083 Thujopsene 1434 C15H24 204
    1084 Selina-4(15),5-diene 1433 C15H24 204
    1085 Pacifigorgia-2(10),11-diene 1435 C15H24 204
    1086 trans-a-Bergamotene 1434 C15H24 204
    1087 a-Pinguisene 1436 C15H24 204
    1088 b-Sesquifenchene 1437 C15H24 204
    1089 Sesquisabinene A 1435 C15H24 204
    1090 Calarene 1437 C15H24 204
    1091 Cubeb-11-ene 1445 C15H24 204
    1092 b-Gorgonene 1440 C15H24 204
    1093 a-Maalinene 1440 C15H24 204
    1094 Cyclofarnesa-5(14),8,10-triene 1441 C15H24 204
    1095 a-Guaiene 1440 C15H24 204
    1096 Acora-3,9-diene 1442 C15H24 204
    1097 Aromadendrene 1443 C15H24 204
    1098 Brasila-1(6),5(10)-diene 1442 C15H24 204
    1099 Isobazzanene 1442 C15H24 204
    1100 Guaia-6,9-diene 1443 C15H24 204
    1101 Nardosina-7,9,11-triene 1444 C15H22 202
    1102 4aH,10aH-Guaia-1(5),6-diene 1445 C15H24 204
    1103 Isogermacrene D 1445 C15H24 204
    1104 Selina-5,11-diene 1444 C15H24 204
    1105 Eremophila-1(10),6-diene 1445 C15H24 204
    1106 b-Barbatene 1445 C15H24 204
    1107 Cadina-4,11-diene 1458 C15H24 204
    1108 Erythrodiene 1446 C15H24 204
    1109 epi-b-Santalene 1446 C15H24 204
    1110 Sesquisabinene B 1446 C15H24 204
    1111 Seychellene 1447 C15H24 204
    1112 Cadina-3,5-diene 1448 C15H24 204
    1113 (E)-b-Farnesene 1446 C15H24 204
    1114 4bH,10aH-Guaia-1(5),6-diene 1448 C15H24 204
    1115 Selina-4(15),6-diene 1450 C15H24 204
    1116 a-Himachalene 1450 C15H24 204
    1117 Prezizaene 1452 C15H24 204
    1118 Bourbon-7(11)-ene 1454 C15H24 204
    1119 a-Humulene 1455 C15H24 204
    1120 e-Muurolene 1455 C15H24 204
    1121 a-Panasinsene 1455 C15H24 204
    1122 Zizaene 1456 C15H24 204
    1123 a-Neoclovene 1456 C15H24 204
    1124 Valerena-4,7(11)-diene 1456 C15H24 204
    1125 Acora-3,10(14)-diene 1457 C15H24 204
    1126 Selina-4(15),7-diene 1457 C15H24 204
    1127 b-Spathulene 1457 C15H22 202
    1128 Muurola-4,11-diene 1458 C15H24 204
    1129 Selina-2,4-diene 1462 C15H24 204
    1130 (Z,Z)-a-Farnesene 1460 C15H24 204
    1131 b-Santalene 1460 C15H24 204
    1132 7bH,10bH-Cadina-1(6),4-diene 1460 C15H24 204
    1133 Rotundene 1461 C15H24 204
    1134 Selina-3,7-diene 1460 C15H24 204
    1135 Striatene 1458 C15H24 204
    1136 allo-Aromadendrene 1462 C15H24 204
    1137 Aromadendr-9-ene 1463 C15H24 204
    1138 a-Patchoulene 1467 C15H24 204
    1139 a-Acoradiene 1464 C15H24 204
    1140 Carota-5,8-diene 1465 C15H24 204
    1141 b-Acoradiene 1465 C15H24 204
    1142 4,5-di-epi-Aristolochene 1470 C15H24 204
    1143 Selina-4,7-diene 1469 C15H24 204
    1144 2-epi-(E)-b-Caryophyllene 1467 C15H24 204
    1145 g-Muurolene 1474 C15H24 204
    1146 Amorpha-4,11-diene 1472 C15H24 204
    1147 7aH,10bH-Cadina-1(6),4-diene 1472 C15H24 204
    1148 ar-Curcumene 1473 C15H22 202
    1149 Eudesma-1,4(15),11-triene 1472 C15H22 202
    1150 Eudesma-2,4,11-triene 1471 C15H22 202
    1151 g-Gurjunene 1472 C15H24 204
    1152 Ishwarane 1468 C15H24 204
    1153 Valenca-2,9,11-trIene 1473 C15H22 202
    1154 b-Chamigrene 1474 C15H24 204
    1155 (3E,6Z)-a-Farnesene 1475 C15H24 204
    1156 Selina-4,11-diene 1475 C15H24 204
    1157 b-Microbiotene 1473 C15H24 204
    1158 a-Amorphene 1477 C15H24 204
    1159 g-Curcumene 1475 C15H24 204
    1160 Herbertene 1476 C15H22 202
    1161 Zierene 1476 C15H22 202
    1162 a-Neocallitropsene 1475 C15H24 204
    1163 Amorpha-4,7(11)-diene 1476 C15H24 204
    1164 5-epi-Aristolochene 1477 C15H24 204
    1165 Isobicyclogermacrene 1477 C15H24 204
    1166 b-Neoclovene 1475 C15H24 204
    1167 trans-b-Bergamotene 1480 C15H24 204
    1168 g-Himachalene 1479 C15H24 204
    1169 Laurene 1483 C15H20 200
    1170 Germacrene D 1479 C15H24 204
    1171 (3Z,6E)-a-Farnesene 1480 C15H24 204
    1172 a-Vetispirene 1481 C15H22 202
    1173 e-Cadinene 1483 C15H24 204
    1174 g-Humulene 1483 C15H24 204
    1175 Isolepidozene 1483 C15H24 204
    1176 cis-Eudesma-6,11-diene 1484 C15H24 204
    1177 Nardosina-9,11-diene 1484 C15H24 204
    1178 Nardosina-1(10),11-diene 1484 C15H24 204
    1179 Eudesma-3,5,11-triene 1485 C15H22 202
    1180 Aristolochene 1486 C15H24 204
    1181 Eremophilene 1486 C15H24 204
    1182 d-Selinene 1490 C15H24 204
    1183 b-Vetispirene 1486 C15H22 202
    1184 Bicyclosesquiphellandrene 1487 C15H24 204
    1185 b-Selinene 1486 C15H24 204
    1186 g-Amorphene 1492 C15H24 204
    1187 allo-Aromadendr-9-ene 1489 C15H24 204
    1188 Eremophila-1(10),7-diene 1488 C15H24 204
    1189 Selina-3,5-diene 1486 C15H24 204
    1190 Zingiberene 1489 C15H24 204
    1191 b-Alaskene 1495 C15H24 204
    1192 Ledene 1491 C15H24 204
    1193 Drim-8(12)-ene 1497 C15H26 206
    1194 Valencene 1494 C15H24 204
    1195 epi-Zonarene 1494 C15H24 204
    1196 (Z)-a-Bisabolene 1494 C15H24 204
    1197 a-Selinene 1494 C15H24 204
    1198 Bicyclogermacrene 1494 C15H24 204
    1199 Caparratriene 1493 C15H26 206
    1200 Eudesma-2,4(15),11-triene 1495 C15H22 202
    1201 Hinesene 1495 C15H24 204
    1202 a-Muurolene 1496 C15H24 204
    1203 Aciphyllene 1495 C15H24 204
    1204 a-Cuprenene 1497 C15H24 204
    1205 Cuparene 1498 C15H22 202
    1206 g-Patchoulene 1497 C15H24 204
    1207 e-Amorphene 1498 C15H24 204
    1208 g-Guaiene 1499 C15H24 204
    1209 b-Pinguisene 1500 C15H24 204
    1210 d-Amorphene 1499 C15H24 204
    1211 (E,E)-a-Farnesene 1498 C15H24 204
    1212 1aH,10aH-Guaia-4,6-diene 1500 C15H24 204
    1213 b-Himachalene 1500 C15H24 204
    1214 D7(14)-ar-Himachalene 1501 C15H20 200
    1215 b-Bisabolene 1503 C15H24 204
    1216 a-Chamigrene 1503 C15H24 204
    1217 Eremophila-1(10),8,11-triene 1504 C15H22 202
    1218 Germacrene A 1503 C15H24 204
    1219 Isorotundene 1503 C15H24 204
    1220 a-Bulnesene 1503 C15H24 204
    1221 b-Curcumene 1503 C15H24 204
    1222 Drimenene 1503 C15H24 204
    1223 Pseudowiddrene 1503 C15H24 204
    1224 a-Alaskene 1512 C15H24 204
    1225 (Z)-g-Bisabolene 1505 C15H24 204
    1226 g-Cadinene 1507 C15H24 204
    1227 Nootkatene 1512 C15H22 202
    1228 Cyclobazzanene 1514 C15H24 204
    1229 cis-Calamenene 1517 C15H22 202
    1230 b-Sesquiphellandrene 1516 C15H24 204
    1231 D7,8-ar-Himachalene 1518 C15H20 200
    1232 7-epi-a-Selinene 1519 C15H24 204
    1233 b-Bazzanene 1519 C15H24 204
    1234 d-Cadinene 1520 C15H24 204
    1235 (E)-g-Bisabolene 1521 C15H24 204
    1236 trans-Calamenene 1517 C15H22 202
    1237 Zonarene 1521 C15H24 204
    1238 b-Cadinene 1526 C15H24 204
    1239 g-Cuprenene 1523 C15H24 204
    1240 Spirovetiva-1(10),7(11)-diene 1523 C15H24 204
    1241 g-Vetivenene 1525 C15H22 202
    1242 Cadina-1,4-diene 1523 C15H24 204
    1243 w-Cadinene 1526 C15H24 204
    1244 a-Calacorene 1527 C15H20 200
    1245 Eremophila-1(10),7(11)-diene 1527 C15H24 204
    1246 ar-Himachalene 1528 C15H22 202
    1247 (E)-a-Bisabolene 1530 C15H24 204
    1248 5-epi-Laurene 1531 C15H20 200
    1249 1,4-Dimethylazulene 1532 C12H12 156
    1250 Selina-4(15),7(11)-diene 1534 C15H24 204
    1251 a-Cadinene 1534 C15H24 204
    1252 w-Amorphene 1540 C15H24 204
    1253 d-Cuprenene 1546 C15H24 204
    1254 (1(10)E,4Z)-Germacrene B 1543 C15H24 204
    1255 Selina-3,7(11)-diene 1542 C15H24 204
    1256 Germacrene B 1552 C15H24 204
    1257 b-Vetivenene 1552 C15H22 202
    1258 g-Calacorene 1554 C15H20 200
    1259 (3E,7E)-4,8,12-Trimethyltrideca- 1565 C16H26 218
    1,3,7,11-tetraene
    1260 Cadalene 1659 C15H18 198
    1261 Daucalene 1671 C15H18 198
    1262 Chamazulene 1719 C14H16 184
    1263 Guaiazulene 1761 C15H18 198
    1264 6-epi-b-Cubebene 1449 C15H24 204
    1265 e-Cuprenene 1524 C15H24 204
    1266 Gymnomitra-3(15),4-diene 1413 C15H22 202
    1267 Tenuifolene 1570 C15H22 202
    1268 ar-Tenuifolene 1528 C15H20 200
    1269 trans-Eudesma-3,5-diene 1490 C15H24 204
    1270 Pethybrene 1440 C15H24 204
    1271 Premnaspirodiene 1516 C15H24 204
    1272 Spirolepechinene 1450 C15H24 204
    1273 trans-Dauca-4(11),7-diene 1554 C15H24 204
    1274 trans-Dauca-4(11),8-diene 1529 C15H24 204
    1275 Cadina-1(10),3,7(11)-triene 1575 C15H22 202
    1276 7,8-Dehydro-a-acoradiene 1450 C15H22 202
    1277 cis-Muurola-4(15),5-diene 1462 C15H24 204
    1278 Patchoula-2,4(15)-diene 1434 C15H22 202
    1279 Norrotundene 1421 C14H22 190
    1280 cis-b-Guaiene 1488 C15H24 204
    1281 Bisaboia-1,3,5,11-tetraene 1461 C15H24 204
    1282 4-epi-b-Patchoulene 1376 C15H24 204
    1283 d-Patchoulene 1466 C15H24 204
    1284 e-Patchoulene 1473 C15H24 204
    1285 10-epi-Muurola-4,11-diene 1458 C15H24 204
    1286 Dauca-8,11-diene 1431 C15H24 204
    1287 Neotrifaradiene 1365 C15H24 204
    1288 Sandvicene 1399 C15H24 204
    1289 Trifara-9,14-diene 1403 C15H24 204
    1290 cis-Muurola-3,5-diene 1447 C15H24 204
    1291 Pacifigorgia-6,10-diene 1429 C15H24 204
    1292 b-Bulnesene 1558 C15H24 204
    1293 Isocalamenene 1527 C15H22 202
    1294 Myltayl-4(12)-ene 1452 C15H24 204
    1295 3,7-di-epi-Trifara-9,14-diene 1399 C15H24 204
    1296 6-epi-a-Cubebene 1418 C15H24 204
    1297 2-Sterpurene 1351 C15H24 204
    1298 a-Corocalen 1602 C15H20 200
    1299 Lactarazulene 1796 C15H16 196
    1300 Prenyllimonene (Isomer 1) 1436 C15H24 204
    1301 Prenyllimonene (Isomer 2) 1450 C15H24 204
    1302 Cadina-1(10),7(11)-diene 1538 C15H24 204
    1303 Elema-1,3,7-triene 1346 C15H24 204
    1304 7-epi-Cadina-1(10),11-diene 1525 C15H24 204
    1305 Cadina-1(10),11-diene 1480 C15H24 204
    1306 Vetivazulene 1790 C15H18 198
    1307 Mintsulphide 1734 C15H24S 236
    1308 Brasila-1,10-diene 1307 C15H24 204
    1309 Drim-8-ene 1442 C15H26 206
    1310 Selina-4(15),7,11-triene 1469 C15H22 202
    1311 5,6-Dehydroalaskene 1371 C15H22 202
    1312 (all-Z)-6,9,12,15-Heneicosatetraene 2048 C21H36 288
    1313 Isoperillene 1073 C10H14O 150
    1314 (E)-Cinnamyl isovalerate 1641 C14H18O2 218
    1315 (E)-Cinnamyl isobutyrate 1543 C13H16O2 204
    1316 (E)-Cinnamyl propionate 1500 C12H14O2 190
    1317 (Z)-Isobutyl cinnamate 1593 C13H16O2 204
    1318 Phenylethyl tiglate 1547 C13H16O2 204
    1319 7-epi-Eremophila-1(10),8,11-triene 1508 C15H22 202
    1320 5-Hydroxymarsupellyl acetate 1814 C17H26O3 278
    1321 Marsupellyl acetate 1681 C17H26O2 262
    1322 4-epi-Marsupellyl acetate 1733 C17H26O2 262
    1323 (E)-Methyl p-methoxycinnamate 1625 C11H12O3 192
    1324 (Z)-Methyl p-methoxycinnamate 1543 C11H12O3 192
    1325 4-epi-Marsupellol 1614 C15H24O 220
    1326 (Z)-Cinnamyl propionate 1552 C12H14O2 190
    1327 (E)-Isobutyl cinnamate 1633 C13H16O2 204
    1328 Methyl 4-methoxymandelate 1511 C10H12O4 196
    1329 (E)-Isoamyl cinnamate 1697 C14H18O2 218
    1330 Pentadecanoic acid 1823 C15H30O2 242
    1331 Methyl o-methoxybenzoate 1300 C9H10O3 166
    1332 Patchenol 1305 C11H18O 166
    1333 Syringa aldehyde 1599 C9H10O4 182
    1334 Methyl 3-methylorsellinate 1674 C10H12O4 196
    1335 Dihydroactinidiolide 1487 C11H16O2 180
    1336 b-Ionone epoxide 1460 C13H20O2 208
    1337 Oxoisophorone 1111 C9H12O2 152
    1338 Sabina ketone 1132 C9H14O 138
    1339 2,6-Di-tert-butyl-4-methylphenol 1492 C15H24O 220
    1340 Cadin-1(10)-ene 5,11-oxide 1574 C15H24O 220
    1341 6,11-Epoxyisodaucane 1463 C15H26O 222
    1342 3-Acetoxy-b-ionone 1752 C15H22O3 250
    1343 Nardosina-7,9-dien-11-ol 1596 C15H24O 220
    1344 Porosadienol 1627 C15H24O 220
    1345 a-Ionone epoxide (Isomer 2) 1512 C13H20O2 208
    1346 Cabreuva oxide A 1437 C15H24O 220
    1347 Cabreuva oxide B 1452 C15H24O 220
    1348 Cabreuva oxide C 1456 C15H24O 220
    1349 (E)-o-Methoxycinnamaldehyde 1477 C10H10O2 162
    1350 (Z)-o-Methoxycinnamaldehyde 1408 C10H10O2 162
    1351 Hydrocinnamyl acetate 1336 C11H14O2 178
    1352 N-Methyl methyl anthranilate 1372 C9H11O2N 165
    1353 Abietal 2261 C20H30O 286
    1354 trans-Totarol 2241 C20H30O 286
    1355 Dehydrogeosmin 1362 C12H20O 180
    1356 1bH,5aH,7bH-Guaia-3,10(14)-dien- 1646 C15H24O 220
    11-ol
    1357 9a,11-Epoxy-1bH,5aH,7bH,9bH- 1587 C15H22O 218
    guaia-3,10(14)-diene
    1358 4-(4-Hydroxyphenyl)-2-butanone 1508 C10H12O2 164
    1359 15-Norlabdan-8-ol 1943 C19H36O 280
    1360 Oxoisoambrox 1819 C16H26O2 250
    1361 Sclareolide 2022 C16H24O3 264
    1362 1-Decanol 1264 C10H22O 158
    1363 Amberone 1810 C17H26O 246
    1364 Methyl arachidonate 2217 C21H34O2 318
    1365 Cyclomyltaylan-15-ol 1641 C15H24O 220
    1366 Tridenson 1633 C15H26O 222
    1367 Tridensenal 1617 C15H26O 222
    1368 6b-Acetoxyeudesm-4(15)-en-7b-ol 1898 C18H30O2 278
    1369 Tridensenone 1815 C15H20O 216
    1370 2,6,6-Trimethylcyclohexanone 1023 C9H16O 140
    1371 2,6,6-Trimethylcyclohex-2-enone 1045 C9H14O 138
    1372 Acetoxycedren-13-ol 1782 C17H26O2 262
    1373 4-Isopropylcyclohexanol (Isomer 1) 1126 C9H18O 142
    1374 3-Hydroxy-4-methoxybenzyl 1421 C8H10O3 154
    alcohol
    1375 a-Ambrinol (Isomer 1) 1382 C13H22O 194
    1376 a-Ambrinol (Isomer 2) 1410 C13H22O 194
    1377 Thymohydroquinone 1509 C10H14O2 166
    1378 Oreodaphnenol 1484 C15H24O 220
    1379 Ambrox 1747 C16H28O 236
    1380 4-Isopropylphenol 1201 C9H12O 136
    1381 Scopoletine 1888 C10H8O4 192
    1382 2,5-Dimethoxy-4-isopropyltoluene 1400 C12H18O2 194
    1383 Silphiperfol-5-en-3-one 1533 C15H22O 218
    1384 Clovenol 1575 C15H24O 220
    1385 trans-6-Hydroxyisocalamenene 1782 C15H22O 218
    1386 1,4-trans-6-Methoxyisocalamenene 1722 C16H24O 232
    1387 Non-1-ene 837 C9H18 126
    1388 Mintoxide 1565 C15H24O 220
    1389 6-Methylheptan-2,4-dione 975 C8H14O2 142
    1390 5-Methylheptan-2,4-dione 966 C8H14O2 142
    1391 2,2-Dimethyl-7-isobutyl-2H,5H- 1770 C14H18O3 234
    pyrano[4.3-b]pyran-5-one
    1392 2,2-Dimethyl-7-secbutyl-2H,5H- 1764 C14H18O3 234
    pyrano[4.3-b]pyran-5-one
    1393 Cyclo-b-ionone 1329 C13H20O 192
    1394 Germacra-4(15),5,10(14)-trien-1a-ol 1680 C15H24O 220
    1395 Eudesma-4(15),7-dien-1b-ol 1671 C15H24O 220
    1396 Cadina-4,10(14)-dien-1a-ol 1662 C15H24O 220
    1397 b-Calacorene 1541 C15H20 200
    1398 1a,10a-Epoxyamorph-4-ene 1569 C15H24O 220
    1399 Muurola-4,10(14)-dien-1-ol 1626 C15H24O 220
    1400 Caryophylla-3(15),7(14)-dien-6-ol 1635 C15H24O 220
    1401 4(15)-Dehydroglobulol 1597 C15H24O 220
    1402 trans-Bisabola-1(6),10-dien-2,3-diol 1758 C15H26O2 238
    1403 6,10-Epoxybisabol-2-en-12-al 1664 C15H24O2 236
    1404 6,10-Epoxybisabol-3-en-12-al 1677 C15H24O2 236
    1405 11-epi-6,10-Epoxybisabol-3-en-12- 1649 C15H24O2 236
    al
    1406 Acora-3,5-dien-11-ol 1574 C15H24O 220
    1407 Acora-2,4(15)-dien-11-ol 1616 C15H24O 220
    1408 7-epi-Bisabol-1-one 1718 C15H24O 220
    1409 (E)-trans-a-Bergamota-2,10-dien-12- 1679 C15H22O 218
    al
    1410 Helifolen-12-al (syn-syn-syn) 1611 C16H24O 232
    1411 Italicene ether 1531 C15H24O 220
    1412 7-epi-b-Bisabolol 1657 C15H26O 222
    1413 Bisabol-1-one 1712 C15H24O 220
    1414 Humulene epoxide 1 1593 C14H22O 206
    1415 10-epi-Italicene ether 1511 C15H24O 220
    1416 3-Hydroxybisabola-1(6),10-dien-2- 1748 C15H24O2 236
    one
    1417 b-Bisabolol 1659 C15H26O 222
    1418 10-epi-Junenol 1581 C15H26O 222
    1419 Junenol 1617 C15H26O 222
    1420 1,10-di-epi-Cubenol 1615 C15H26O 222
    1421 Carquejyl acetate 1284 C12H16O2 192
    1422 (E)-Dendrolasin 1566 C15H22O 218
    1423 Artemisyl acetate 1164 C12H20O2 196
    1424 Artedouglasia oxide C 1507 C15H22O3 250
    1425 Artedouglasia oxide A 1517 C15H22O3 250
    1426 1-Undecanol 1363 C11H24O 172
    1427 Laciniata furanone H 1530 C15H22O3 250
    1428 Lanciniata furanone F 1514 C15H22O3 250
    1429 Artedouglasia oxide B 1561 C15H22O3 250
    1430 Artedouglasia oxide D 1542 C15H22O3 250
    1431 Cymen-8-ol 1169 C10H14O 150
    1432 2,2,9-Trimethyl-1,6- 1079 C10H14O2 166
    dioxaspiro[4.4]nona-3,8-diene
    1433 Menthyl formate 1230 C11H20O2 184
    1434 Folifolone 1090 C10H14O 150
    1435 Santolina alcohol 1029 C10H18O 154
    1436 cis-p-Mentha-1(7),8-dien-2-ol 1217 C10H16O 152
    1437 trans-p-Mentha-1(7),8-dien-2-ol 1176 C10H16O 152
    1438 trans-p-Menth-2-en-1-ol 1116 C10H18O 154
    1439 cis-p-Mentha-2,8-dien-1-ol 1125 C10H16O 152
    1440 trans-p-Mentha-2,8-dien-1-ol 1113 C10H16O 152
    1441 Dehydrosabinaketone 1100 C9H12O 136
    1442 4-Hydroxy-4-methylcyclohex-2- 1089 C7H10O2 126
    enone
    1443 2-(1-Hydroxyethyl)-5-methyl-5- 1054 C9H16O2 156
    vinyltetrahydrofuran
    1444 trans-Arbusculone 1036 C9H14O2 154
    1445 Lavender lactone 1006 C7H10O2 126
    1446 Pulegone epoxide 1238 C10H16O2 168
    1447 3-Methylcyclohexanone 928 C7H12O 112
    1448 trans-Linalool oxide acetate 1274 C12H20O3 212
    1449 Fragranyl acetate 1331 C11H18O2 182
    1450 6-Methyl-6-(3-methylphenyl)-2- 1609 C15H22O 218
    heptanone
    1451 3-exo-Acetoxybornyl acetate 1520 C14H22O4 254
    1452 3-exo-Acetoxyborneol 1402 C12H20O3 212
    1453 3-exo-Hydroxybornyl acetate 1393 C12H20O3 212
    1454 Lavandulyl acetate 1275 C12H20O2 196
    1455 5-Hydroxymarsupellol 1776 C15H24O2 236
    1456 b-Isolongibornene 1440 C15H24 204
    1457 Geranyl propionate 1486 C13H22O2 210
    1458 (E)-Isosafrol 1356 C10H10O2 162
    1459 2,3-Dihydrofarnesol 1674 C15H28O 224
    1460 Methyl 4-hydroxymandelate 1572 C9H10O4 182
    1461 Methyl 3-(4-methoxyphenyl)- 1494 C11H14O3 194
    propionate
    1462 Methyl 3,5-dimethoxyphenylacetate 1603 C11H14O4 210
    1463 2a-Hydroxyamorpha-4,7(11)-diene 1678 C15H24O 220
    1464 l-Hepten-3-one 956 C7H12O 112
    1465 Ferulyl angelate 1682 C15H20O3 248
    1466 Undecanal 1290 C11H22O 170
    1467 n-Hexadecanoic acid 1951 C16H32O2 256
    1468 n-Tetradecanoic acid 1748 C14H28O2 228
    1469 n-Dodecanoic acid 1554 C12H24O2 200
    1470 n-Decanal 1180 C10H20O 156
    1471 Axenol (Gleenol) 1574 C15H26O 222
    1472 epi-Methyl jasmonate 1637 C13H20O3 224
    1473 5-Ethylcyclopent-1-enecarbaldehyde 1010 C8H12O 124
    1474 Methyl hexanoate 905 C7H14O2 130
    1475 Methyl undecanoate 1400 C12H24O2 200
    1476 Methyl dodecanoate 1500 C13H26O2 214
    1477 Methyl tridecanoate 1600 C14H28O2 228
    1478 Methyl myristoleate 1683 C15H28O2 240
    1479 (Z)-Methyl pentadec-10-enoate 1786 C16H30O2 254
    1480 Methyl palmitoleate 1877 C17H32O2 268
    1481 (Z)-Methyl Heptadec-10-enoate 1978 C18H34O2 282
    1482 Methyl heptadecanoate 2001 C17H34O2 270
    1483 Methyl oleate 2082 C19H36O2 296
    1484 Dihydroedulan 1290 C13H22O 194
    1485 2-Methylbenzofuran 1149 C9H8O 132
    1486 (all-Z)-Methyl Docosa- 2395 C23H34O2 342
    4,7,10,13,16,19-hexaenoate
    1487 (Z,Z)-Methyl docosa-13,16-dienoate 2433 C23H42O2 350
    1488 Methyl erucate 2440 C23H44O2 352
    1489 Methyl behenate 2459 C23H46O2 354
    1490 Methyl tricosanoate 2558 C24H48O2 368
    1491 Methyl nervonate 2650 C25H48O2 380
    1492 (Z)-Methyl eicosa-11-enoate 2248 C21H40O2 324
    1493 Methyl lignocerate 2695 C25H50O2 382
    1494 Methyl arachidate 2306 C21H42O2 326
    1495 Methyl heneicosanoate (C-21) 2412 C22H44O2 340
    1496 Methyl stearate 2104 C19H38O2 298
    1497 (all-Z)-Methyl eicosa-11,14-dienoate 2243 C22H40O2 336
    1498 Methyl elaidate 2084 C19H36O2 296
    1499 Methyl linolenate 2036 C19H32O2 292
    1500 Methyl linoleate 2046 C19H34O2 294
    1501 Methyl palmitate 1901 C17H34O2 270
    1502 Methyl pentadecanoate 1796 C16H32O2 256
    1503 Methyl myristate 1700 C15H30O2 242
    1504 Methyl octanoate 1100 C91H8O2 158
    1505 Methyl nonanoate 1208 C10H20O2 172
    1506 Methyl decanoate 1300 C11H22O2 186
    1507 (3Z,9E)-Isoligustilide 1824 C12H14O2 190
    1508 (Z)-3-Butyliden-4,5,6,7- 1697 C12H16O2 192
    tetrahydrophthalide
    1509 Neophytadiene (Isomer 1) 1807 C20H38 278
    1510 Neophytadiene (Isomer 2) 1830 C20H38 278
    1511 Neophytadiene (Isomer 3) 1849 C20H38 278
    1512 Eudesm-3-ene 6,7-oxide 1787 C15H24O 220
    1513 Eudesma-3,7(11)-dien-8-one 1745 C15H22O 218
    1514 5-Methylfurfural 941 C6H6O2 110
    1515 g-Costol 1732 C15H24O 220
    1516 a-Costol 1761 C15H24O 220
    1517 b-Costol 1754 C15H24O 220
    1518 Dehydrocostunolide 1956 C15H18O2 230
    1519 Dihydrodehydrocostus lactone 1903 C15H20O2 232
    1520 Eudesma-4(15),11-dien-8-one 1643 C15H22O 218
    1521 (E)-15,16-Bisnorlabda-8(17),12- 2051 C18H28O 260
    dien-14-al
    1522 (E)-15,16-Bisnorlabda-8(17),11- 1958 C18H28O 260
    dien-13-one
    1523 Albicanol 1736 C16H28O 236
    1524 g-Bicyclofarnesal 1656 C15H24O 220
    1525 trans-6,6,10-Trimethyl-2-decalone 1505 C13H22O 194
    1526 Coronarin E 2095 C20H28O 284
    1527 10-Hydroxy-4-oplopanone 1708 C15H26O2 238
    1528 Valerenic acid 1843 C15H22O2 234
    1529 Vulgarone A 1580 C15H22O 218
    1530 Artemisiatriene 923 C10H16 136
    1531 2-Methylbutyl octanoate 1427 C13H26O2 214
    1532 Hexyl hexanoate 1363 C12H24O2 200
    1533 (E)-2-Decenal 1240 C10H18O 154
    1534 2-methylbutyl hexanoate 1235 C11H22O2 186
    1535 n-Hexyl 2-methylbutanoate 1220 C11H22O2 186
    1536 n-Hexyl butanoate 1176 C10H20O2 172
    1537 (E)-2-Heptenal 942 C7H12O 112
    1538 Fenchyl acetate (Isomer) 1224 C12H20O2 196
    1539 11-Nordrim-8-en-12-al 1609 C14H22O 206
    1540 Undecanoic acid 1452 C11H22O2 186
    1541 Allyl-2,4-di-acetoxybenzene 1592 C13H14O4 234
    1542 n-Decane 993 C10H22 142
    1543 n-Dodecane 1200 C12H26 170
    1544 n-Tridecane 1300 C13H28 184
    1545 n-Tetradecane 1392 C14H30 198
    1546 n-Pentadecane 1500 C15H32 212
    1547 n-Hexadecane 1600 C16H34 226
    1548 n-Heptadecane 1700 C17H36 240
    1549 n-Octadecane 1792 C18H38 254
    1550 n-Eicosane (C-20) 2000 C20H42 282
    1551 n-Heneicosane (C-21) 2100 C21H44 296
    1552 n-Docosane (C-22) 2200 C22H46 310
    1553 n-Tricosane (C-23) 2301 C23H48 324
    1554 n-Tetracosane (C-24) 2400 C24H50 338
    1555 n-Pentacosane (C-25) 2498 C25H52 352
    1556 n-Hexacosane (C-26) 2598 C26H54 366
    1557 Verbenene 982 C10H14 134
    1558 trans-Chrysanthenyl acetate 1214 C12H18O2 194
    1559 trans-Chrysanthenol 1096 C10H16O 152
    1560 (Z)-2,6-Dimethylocta-1,5,7-trien-3- 1048 C10H16O 152
    ol
    1561 (E)-2,6-Dimethylocta-1,5,7-trien-3- 1058 C10H16O 152
    ol
    1562 Dihydrodiplophylline 1896 C15H22O2 234
    1563 Diplophylline 1965 C15H20O2 232
    1564 Ginsensene 1353 C15H24 204
    1565 2-Methyl-2,5-divinyltetrahydrofuran 900 C9H14O 138
    1566 5-Ethyl-2-methyl-2- 893 C9H16O 140
    vinyltetrahydrofuran
    1567 (all-E)-1,7-Dimethylcyclodeca- 1274 C12H18 162
    1,4,7-triene
    1568 Salviadienol 1545 C15H24O 220
    1569 Torilenol 1599 C13H20O 192
    1570 Betaer-13-ene 2040 C20H32 272
    1571 Ethylbenzene 843 C8H10 106
    1572 4-epi-11-Noraristola-9,11-diene 1399 C14H20 188
    1573 4-epi-11-Noraristola-1,9,11-triene 1419 C14H18 186
    1574 4-epi-11-Noraristola-1(10),11-diene 1409 C14H20 188
    1575 4-Ethylguiacol 1257 C9H12O2 152
    1576 2-Hydroxy-4-methoxyacetophenone 1294 C9H10O3 166
    1577 4-Vinylanisol 1134 C9H10O 134
    1578 p-Ethylanisol 1099 C9H12O 136
    1579 1-Acetoxy-4-ethylbenzene 1238 C10H12O2 164
    1580 Tetradecanal 1596 C14H28O 212
    1581 4-Ethylphenol 1139 C8H10O 122
    1582 Dehydropinguisenol 1800 C15H20O2 232
    1583 Fusicocca-2,5-diene 2020 C20H32 272
    1584 Crispatanolide 1760 C15H22O2 234
    1585 (+)-Himachala-2,4-diene 1433 C15H24 204
    1586 Polygodial 1839 C15H22O2 234
    1587 9-epi-Polygodial 1960 C15H22O2 234
    1588 Dihydrofrullanolide 1874 C15H22O2 234
    1589 Eudesma-3,11-dien-8-one 1666 C15H22O 218
    1590 5,8a-Dimethyl-3,4,4a,7,8,8a- 1464 C12H18O 178
    hexahydro-1H-naphthalen-2-one
    1591 8a-Hydroxyeudesma-3,11-diene 1668 C15H24O 220
    1592 6,11-Epoxyeudesmane 1521 C15H26O 222
    1593 Eudesma-5,7(11)-diene 1543 C15H24 204
    1594 6b-Hydroxyeudesm-11-ene 1643 C15H26O 222
    1595 6a-Hydroxyeudesm-11-ene 1598 C15H26O 222
    1596 6,7-seco-Eudesm-7(11)-en-6-al 1615 C15H26O 222
    1597 Ipsenol 1083 C10H18O 154
    1598 Phytane 1808 C20H42 282
    1599 Farnesane 1375 C15H32 212
    1600 b-n-Octyl-g-butanolide 1655 C12H22O2 198
    1601 Crocetane 1810 C20H42 282
    1602 Pristane 1706 C19H40 268
    1603 cis-Eudesma-4,11-dien-8-ol 1648 C15H24O 220
    1604 Bisabola-1(6),2,10Z-trien-12-al 1733 C15H22O 218
    1605 8,9-Epoxyselina-4,11-diene 1597 C15H22O 218
    1606 Eudesma-4(15),11-dien-5-ol 1629 C15H24O 220
    1607 cis-Eudesma-4(15),11-dien-5-ol 1623 C15H24O 220
    1608 Pentadecanal 1702 C15H30O 226
    1609 3-Methylbutanolide 909 C5H8O2 100
    1610 2-n-Propyl-g-butanolide 1100 C7H12O2 128
    1611 2-n-Pentyl-g-butanolide 1311 C9H16O2 156
    1612 2-Ethylbutanolide 1000 C6H10O2 114
    1613 2-Methylbutanolide 902 C5H8O2 100
    1614 4-Allyl-g-butanolide 1090 C7H10O2 126
    1615 d-Tetradecalactone 1893 C14H26O2 226
    1616 d-Tridecanolide 1786 C13H24O2 212
    1617 d-Dodecanolide 1675 C12H22O2 198
    1618 g-n-Tetradecyl-g-butanolide 2720 C18H34O2 282
    1619 d-Hexaolide 1044 C6H10O2 114
    1620 N-2-[(4-Hydroxyphenyl)-ethyl]- 2325 C13H17O2N 219
    tiglamide
    1621 4-Hydroxy-b-ionone 1628 C13H20O2 208
    1622 (E)-Megastigm-7-en-3,9-dione (t) 1572 C13H20O2 208
    1623 a-Helmiscapene 1447 C15H24 204
    1624 Methyl 2-(2-methylbutyroxy)-3- 1339 C12H22O4 230
    methylpentanoate
    1625 7,8-Dihydro-b-ionol 1431 C13H24O 196
    1626 Dodecyl acetate 1585 C14H28O2 228
    1627 (Z)-Heptadec-8-ene 1666 C17H34 238
    1628 cis-Dracunculifolione 1500 C15H24O 220
    1629 Italicen-13-ol 1670 C15H24O 220
    1630 10-epi-cis-Dracunculifoliol 1533 C15H26O 222
    1631 cis-Dracunculifoliol 1534 C15H26O 222
    1632 trans-Dracunculifoliol 1581 C15H26O 222
    1633 3-Hydroxy-b-ionone 1647 C13H20O2 208
    1634 3-Hydroxy-5,6-dihydro-b-ionone 1609 C13H22O2 210
    1635 (E)-b-Santalol 1680 C15H24O 220
    1636 o-Cymene 976 C10H14 134
    1637 Methyl 11-methyltridecanoate 1668 C15H30O2 242
    1638 Libocedrol 2326 C22H30O4 358
    1639 Aristol-1(10)-en-12-ol 1712 C15H24O 220
    1640 Costunolide 1914 C15H20O2 232
    1641 7-Hydroxyeudesm-4-en-6-one 1703 C15H24O2 236
    1642 Aristol-1(10)-en-12-al 1704 C15H22O 218
    1643 Methyl 10-methyldodecanoate 1575 C14H28O2 228
    1644 Dotriacontane 3200 C32H66 450
    1645 Eudesma-4(15),7(11),9-trien-12- 1971 C15H18O2 230
    olide
    1646 Isogermafurenolide 1867 C15H20O2 232
    1647 Chloranthalactone A 1941 C15H16O2 228
    1648 Ethyl decanoate 1375 C12H24O2 200
    1649 Ethyl palmitate 1954 C18H36O2 284
    1650 7,11-Epoxymegastigm-5-en-9-one 1551 C13H20O2 208
    1651 Neoiso-isopulegol 1164 C10H18O 154
    1652 b-Ionol 1400 C13H22O 194
    1653 8-Hydroxylinalyl tiglate 1760 C15H24O3 252
    1654 (Z)-Methyl 4-(geranyloxy)- 2334 C20H26O3 314
    cinnamate
    1655 (E)-Methyl 4-(geranyloxy)- 2461 C20H26O3 314
    cinnamate
    1656 Tetradecyl acetate 1775 C16H32O2 256
    1657 Benzyl 3-methylbutyrate 1366 C12H16O2 192
    1658 Benzyl 2-methylbutyrate 1360 C12H16O2 192
    1659 Decanoic acid 1347 C10H20O2 172
    1660 n-Octanoic acid 1156 C8H16O2 144
    1661 Dihydromayurone 1591 C14H22O 206
    1662 Ethyl hexadecanoate 1990 C18H36O2 284
    1663 8-Hydroxylinalyl propionate 1551 C13H22O3 226
    1664 4-Acetoxy-3-methoxyacetophenone 1434 C11H12O4 208
    1665 o-Anisaldehyde 1202 C8H8O2 136
    1666 2-Octanone 964 C8H16O 128
    1667 (E)-trans-Bergamotol 1680 C15H24O 220
    1668 Methyl 3-methylpentanoate 853 C7H14O2 130
    1669 Methyl 3,7-dimethyloctanoate 1207 C11H22O2 186
    1670 Methyl 4-methylhexanoate 974 C8H16O2 144
    1671 Muurolan-4,7-oxide 1480 C15H26O 222
    1672 cis-Totarol 2252 C20H30O 286
    1673 4-Butyl-3-methyl-g-butanolide 1252 C9H16O2 156
    1674 Isosaccogynol 1740 C15H22O 218
    1675 Isosaccogynone 1744 C15H20O 216
    1676 Taylorione 1617 C15H22O 218
    1677 2-a-Acetoxy-11-methoxyamorpha- 1846 C18H28O3 292
    4,7-diene
    1678 2-a-Acetoxyamorpha-4,7(11)-dien- 1963 C17H24O3 276
    8-one
    1679 Neryl formate 1265 C11H18O2 182
    1680 Geranyl butyrate 1534 C15H26O2 238
    1681 Nerylpropionate 1451 C14H24O2 224
    1682 Geranyl tiglate 1670 C15H24O2 236
    1683 2-Methylbutyl angelate 1130 C10H18O2 170
    1684 3-Methylbutyl angelate 1125 C10H18O2 170
    1685 Methallyl angelate 1040 C9H14O2 154
    1686 3-Methylbutyl methacrylate 1018 C9H16O2 156
    1687 3-Methylbutyl isobutyrate 994 C9H18O2 158
    1688 3-Methylpentyl isobutyrate 1095 C10H20O2 172
    1689 3-Methylpentyl angelate 1230 C11H20O2 184
    1690 Butyl angelate 1065 C9H16O2 156
    1691 10-Acetoxy-4-oplopanone 1874 C17H28O3 280
    1692 Butyl benzoate 1556 C11H14O2 178
    1693 Propyl benzoate 1347 C10H12O2 164
    1694 Phenylacetonitrile 1085 C8H7N 117
    1695 Hexadecyl acetate 1847 C18H36O2 284
    1696 Octadecyl acetate 2084 C20H40O2 312
    1697 Octadecanal 2012 C18H36O 268
    1698 Hexadecanal 1782 C16H32O 240
    1699 Heptacosane 2700 C27H56 380
    1700 Docosanal 2338 C22H44O 324
    1701 cis-b-Elemene 1381 C15H24 204
    1702 Eicosanal 2170 C20H40O 296
    1703 1-Methyl-3-(2-oxopropyl)-4-(1- 1409 C13H20O 192
    methylethenyl)-cyclohexene
    1704 Ginsenol 1621 C15H26O 222
    1705 4-n-Propylanisol 1254 C10H14O 150
    1706 n-Decyl acetate 1390 C12H24O2 200
    1707 Dimethyl-tetrasulfide 1181 C2H6S4 158
    1708 Dimethyl trisulfide 942 C2H6S3 126
    1709 S,S-Dimethyl dithiocarbonate 935 C3H6OS2 122
    1710 2,5-Diethyltetrahydrofuran 875 C8H16O 128
    1711 Neoiso-isopulegol acetate 1366 C12H20O2 196
    1712 Methyl 2-hydroxy-4-methoxy-6- 1555 C10H12O4 196
    methylbenzoate
    1713 1-Octen-3-yl 3-methylbutyrate 1315 C13H24O2 212
    1714 1-Octen-3-yl 2-methylbutyrate 1310 C13H24O2 212
    1715 Oct-1-en-3-yl butyrate 1266 C12H22O2 198
    1716 1-Octen-3-yl isobutyrate 1223 C12H22O2 198
    1717 l-Octen-3-yl propanoate 1181 C11H20O2 184
    1718 14-Hydroxy-4,5-dihydro-b- 1692 C15H26O 222
    caryophyllene
    1719 14-Hydroxy-b-caryophyllene 1656 C15H24O 220
    1720 4,5-Dihydro-b-caryophyllen-14-al 1610 C15H24O 220
    (Isomer 1)
    1721 4,5-Dihydro-b-caryophyllen-14-al 1621 C15H24O 220
    (Isomer 2)
    1722 4-Desmethylcaryophyll-8(14)-en-5- 1521 C14H22O 206
    one
    1723 Isocaryophyllen-14-al (b-Betulenal) 1630 C15H22O 218
    1724 1-Angeloyloxyverbenone 1694 C15H20O3 248
    1725 4-Hydroxy-2-methylacetophenone 1254 C9H10O2 150
    1726 7-epi-1,2-Dehydrosesquicineole 1460 C15H24O 220
    1727 1,2-Dimethoxybenzene (Veratrol) 1117 C8H10O2 138
    1728 (E)-Isoelemicin 1614 C12H16O3 208
    1729 (Z)-Isoelemicin 1559 C12H16O3 208
    1730 1,2,4-Trimethoxybenzene 1330 C9H12O3 168
    1731 p-Menth-1-en-9-al (Isomer 1) 1188 C10H16O 152
    1732 p-Menth-1-en-9-al (Isomer 2) 1190 C10H16O 152
    1733 (Methoxymethyl)-benzene 964 C8H10O 122
    1734 1,4-Dimethoxybenzene 1132 C8H10O2 138
    1735 6,10,14-Trimethylpentadecan-2-one 1817 C18H36O 268
    1736 (Z)-a-Damascone 1343 C13H20O 192
    1737 Lilac alcohol (2R,2′R,5′S) 1210 C10H18O2 170
    1738 Lilac alcohol (2R,2′S,5′S)) 1196 C10H18O2 170
    1739 Lilac alcohol (2S,2′S,5′S) 1185 C10H18O2 170
    1740 Lilac aldehyde (2R,2′R,5′S) 1146 C10H16O2 168
    1741 Lilac aldehyde (2R,2′S,5′S) 1133 C10H16O2 168
    1742 Lilac aldehyde (2S,2′S,5′S) 1124 C10H16O2 168
    1743 Methyl citronellate 1245 C11H20O2 184
    1744 Myli-4(15)-ene 1418 C15H22 202
    1745 Maali-4(15)-en-1-ol 1624 C15H24O 220
    1746 (E)-Taylopyran 1530 C15H22O 218
    1747 7-epi-Bourbon-3-ene 5,11-oxide 1473 C15H22O 218
    1748 Mylian-3-one 1593 C15H22O 218
    1749 Myli-4(15)-en-3-one 1610 C15H20O 216
    1750 5,5-Dimethyl-1-vinylbicyclo- 931 C10H16 136
    [2.1.1] hexane
    1751 Cara-2,4-diene 900 C10H14 134
    1752 Eudesm-4(15)en-6-one 1616 C15H24O 220
    1753 Eudesm-4-en-6-one 1605 C15H24O 220
    1754 Guaia-3,9-diene 5,11-oxide 1519 C15H22O 218
    1755 Guaia-3,10(14)-diene 5,11-oxide 1555 C15H22O 218
    1756 3-Ethylacetophenone 1260 C10H12O 148
    1757 4-Ethylacetophenone 1240 C10H12O 148
    1758 (6Z,8E)-Megastigma-4,6,8-trien-3- 1553 C13H18O 190
    one
    1759 (E,E)-Megastigma-4,6,8-trien-3-one 1598 C13H18O 190
    1760 Aromadendra-1(10),4(15)-diene 1506 C15H22 202
    1761 Perfora-1,7-diene 1543 C15H24 204
    1762 Guaia-1(10),11-diene 1516 C15H24 204
    1763 Guaia-9,11-diene 1522 C15H24 204
    1764 Norpinguisone 1600 C14H18O2 218
    1765 Methyl norpinguisonate 1776 C15H18O4 262
    1766 Bisabola-1,3,5,7(14)-tetraene 1484 C15H22 202
    1767 Lemnalone 1611 C15H22O 218
    1768 Methyl 2,4-Dimethoxy-6- 1588 C11H14O4 210
    methylbenzoate
    1769 Methyl 6-Methoxy-2-methyl-3,4- 1661 C11H12O5 224
    methylendioxybenzoate
    1770 Methyl 6-Hydroxy-2-methyl-3,4- 1640 C10H10O5 210
    methylendioxybenzoate
    1771 Methyl 3,4,6-trimethoxy-2- 1705 C12H16O5 240
    methylbenzoate
    1772 4-Methoxyphenylacetaldehyde 1255 C9H10O2 150
    1773 Aromadendra-4,9-diene 1534 C15H22 202
    1774 Aromadendra-1(10),4-diene 1462 C15H22 202
    1775 Aromadendra-4,10(14)-diene 1440 C15H22 202
    1776 5,6-Dihydro-1,4-dimethylazulene 1428 C12H14 158
    1777 3,4,5,6-Tetrahydro-1,4- 1246 C12H16 160
    dimethylazulene
    1778 2,3,3a,4,5,6-Hexahydro-1,4- 1447 C12H18O 178
    dimethylazulen-3-ol
    1779 3a-Acetoxyamorpha-4,7(11)-diene 1780 C17H26O2 262
    1780 Amorpha-2,4,7(11)-triene 1449 C15H22 202
    1781 Amorpha-4,7(11)-dien-2-one 1645 C15H22O 218
    1782 2a-Acetoxyamorpha-4,7(11)-diene 1796 C17H26O2 262
    1783 2b-Acetoxyamorpha-4,7(11)-diene 1722 C17H26O2 262
    1784 9a-Hydroxyamorpha-4,7(11)-diene 1680 C15H24O 220
    1785 7b-Hydroxyamorpha-4,11-diene 1615 C15H24O 220
    1786 3a-Hydroxyamorpha-4,7(11)-diene 1665 C15H24O 220
    1787 Amorpha-4,7(11)-dien-3-one 1677 C15H22O 218
    1788 Eudesma-4,11-dien-9-one 1649 C15H22O 218
    1789 2,8-Epoxyamorpha-4,7(11)-diene 1597 C15H22O 218
    1790 5,9-Epoxyamorpha-3,7(11)-diene 1594 C15H22O 218
    1791 n-Tridecanal 1493 C13H26O 198
    1792 (E)-Non-2-en-4-one 306 1098 C9H16O 140
    1793 (E)-3-Methylnon-2-en-4-one 1190 C10H18O 154
    1794 Isotheaspirane (Isomer 1) 1263 C13H22O 194
    1795 Isotheaspirane (Isomer 1) 1279 C13H22O 194
    1796 Chiloscyphone 1576 C15H22O 218
    1797 2-Hydroxy-3,5-dimethoxy-9,10- 2251 C16H16O3 256
    dihydrophenanthrene
    1798 4,5-Dihydroxy-3-methoxy-9,10- 2330 C15H14O3 242
    dihydrophenanthrene
    1799 Isozierene 1556 C15H22 202
    1800 Isogermacrene A 1502 C15H24 204
    1801 Iso-b-elemene 1359 C15H24 204
    1802 n-Decyl butanoate 1567 C14H28O2 228
    1803 g-Palmitolactone 2081 C16H30O2 254
    1804 n-Octyl butanoate 1371 C12H24O2 200
    1805 Benzyl butanoate 1313 C11H14O2 178
    1806 n-Butyl butyrate 970 C8H16O2 144
    1807 n-Heptyl butanoate 1270 C11H22O2 186
    1808 2-Phenylethyl butyrate 1412 C12H16O2 192
    1809 Ethyl 2-phenylhexanoate 1617 C14H20O2 220
    1810 Methyl 4-hydroxybenzoate 1414 C8H8O3 152
    1811 n-Propyl 4-hydroxybenzoate 1584 C10H12O3 180
    1812 n-Octyl hexanoate 1567 C14H28O2 228
    1813 11-b-Hydroxykauren-15-a-yl acetate 2459 C22H34O3 346
    1814 a-Campholenic acid 1304 C10H16O2 168
    1815 5-Acetoxybornan-2-one 1399 C12H18O3 210
    1816 n-Heptadecanal 1908 C17H34O 254
    1817 Ventricos-7(13)-ene 1357 C15H24 204
    1818 Helminthogermacrene 1503 C15H24 204
    1819 allo-Aromadendra-4(15),10(14)- 1457 C15H22 202
    diene
    1820 Methyl 3-phenylpropanoate 1242 C10H12O2 164
    1821 Nepetalactone (Isomer 1) 1331 C10H14O2 166
    1822 (all-E)-Geranylcitronellol 2160 C20H36O 292
    1823 Cyclooctatetraene 837 C8H8 104
    1824 4-(4-Hydroxyphenyl)-butan-2-ol 1518 C10H14O2 166
    1825 Lowry's phenol 1684 C12H16O4 224
    1826 Platyphyllol 1588 C12H16O4 224
    1827 Eugenitine 1944 C12H12O4 220
    1828 Isoeugenitine 1963 C12H12O4 220
    1829 Dihydrocolumellarine 1889 C15H22O2 234
    1830 Myltaylenol 1727 C15H24O 220
    1831 a-Gorgonene 1490 C15H24 204
    1832 Aromadendra-4(15),10(14)dien-1- 1579 C15H22O 218
    ol
    1833 10-epi-Dihydroagarofuran 1520 C15H26O 222
    1834 3,7-Dimethyl-3,7-dihydroxyoct-1- 1198 C10H20O2 172
    ene
    1835 Agarospirol 1635 C15H26O 222
    1836 10a-Hydroxy-12-prenylguai-11-ene 2111 C20H34O 290
    1837 5-Formyl-2-hydroxy-(3- 1617 C12H14O3 206
    methylbutyro)-phenone
    1838 4-Hydroxybenzaldehyde 1316 C7H6O2 122
    1839 1,3,5-Trimethyl-1,3,5-triazin-2,4,6- 1327 C6H9O3N3 171
    trione
    1840 5-Formyl-2-hydroxy-(3-hydroxy-3- 1660 C12H14O4 222
    methylbutyro)-phenone
    1841 Octadecanoic acid 2182 C18H36O2 284
    1842 Longipinanol, high temp. 1563 C15H26O 222
    1843 Artemiseol 970 C10H16O 152
    1844 a-Cyclocitral 1103 C10H16O 152
    1845 (3E,5Z)-Undeca-1,3,5-triene (Isomer 1133 C11H18 150
    2)
    1846 Undeca-1,3,5-triene (Isomer 1) 1117 C11H18 150
    1847 4-(4-Methoxyphenyl)-butan-2-one 1453 C11H14O2 178
    1848 Atranol 1511 C8H8O3 152
    1849 Chloroatranol 1466 C8H703Cl 186
    1850 Myrtenyl methyl ether 1145 C11H18O 166
    1851 8,14-Cedrane oxide 1536 C15H24O 220
    1852 Camphene hydrate 1143 C10H18O 154
    1853 6-Camphenone 1082 C10H14O 150
    1854 Desmethoxyencecalin 1617 C13H14O2 202
    1855 Bisabola-1,3,5,7-tetraene 1554 C15H22 202
    1856 Myltayl-4-ene 1383 C15H24 204
    1857 Gorgon-11-en-4-ol 1617 C15H26O 222
    1858 a-Taylorione 1586 C15H22O 218
    1859 Taylocyclan 1477 C15H22O 218
    1860 Taynudol 1709 C15H22O 218
    1861 Taylofuran 1635 C15H24O2 236
    1862 3-Acetoxytaylorione 1918 C17H24O3 276
    1863 Copalol 2265 C20H34O 290
    1864 3a-Acetoxybicyclogermacrene 1769 C17H26O2 262
    1865 Plagiooxide 1420 C15H26O 222
    1866 Gymnomitr-3(15)-en-5b-ol 1653 C15H24O 220
    1867 5b-Acetoxy-gymnomitr-3(15)-ene 1758 C17H26O2 262
    1868 4b,5b-Diacetoxygymnomitr-3(15)- 1943 C19H28O4 320
    ene
    1869 15-Acetoxygymnomitr-3-ene 1797 C17H26O2 262
    1870 3,15-b-Epoxy-4b- 1875 C17H26O3 278
    acetoxygymnomitrane
    1871 3,15-a-Epoxy-4b- 1887 C17H26O3 278
    acetoxygymnomitrane
    1872 Iso-a-humulene 1474 C15H24 204
    1873 cis-Anethol 1230 C10H12O 148
    1874 Cadina-4,11-dien-15-al 1704 C15H22O 218
    1875 Cadina-4,11-dien-15-ol 1713 C15H26O 222
    1876 a-Barbatenal 1659 C15H22O 218
    1877 15-Nor-3-gymnomitrone 1609 C14H22O 206
    1878 Bergaptene 2023 C12H8O4 216
    1879 Peucedanin 2243 C15H14O4 258
    1880 syn-Copalol 2165 C20H34O 290
    1881 Melanene 1455 C15H24 204
    1882 Panaxene 1312 C15H24 204
    1883 Panaginsene 1336 C15H24 204
    1884 Iso-g-bisabolene 1523 C15H24 204
    1885 Viscida-4,9,14-triene 1862 C20H32 272
    1886 Trichodiene 1523 C15H24 204
    1887 2-Methyl-3-(4-methoxyphenyl)- 1324 C11H14O 162
    prop-2-ene
    1888 Gymnomitr-3(15)-en-12-oic acid 1790 C15H22O2 234
    1889 12-Acetoxygymnomitr-3(15)-ene 1795 C17H26O2 262
    1890 Gymnomitr-3(15)-en-12-al 1627 C15H22O 218
    1891 Scapanol 1586 C15H26O 222
    1892 Hydroxycitronellal 1263 C10H20O2 172
    1893 2-(2-Ethoxyethoxy)-ethanol 985 C6H14O3 134
    1894 Di-(2-hydroxypropyl)-ether 1003 C6H14O3 134
    1895 Benzyl propionate 1231 C10H12O2 164
    1896 2-Methyl-3-(4-isopropylphenyl)- 1433 C13H18O 190
    propanal
    1897 (Z)-b-Curcumen-12-ol 1732 C15H24O 120
    1898 (Z)-b-Phenylethyl cinnamate 2006 C17H16O2 152
    1899 (E)-b-Phenylethyl cinnamate 1123 C17H16O2 252
    1900 Phenylethyl benzoate 1815 C15H14O2 126
    1901 Phenyl ethyl phenylacetate 1868 C16H16O2 240
    1902 Phenyl ethyl propionate 1468 C11H14O2 178
    1903 2-(4-Methoxyphenyl)-5-methoxy- 2237 C16H16O3 256
    2,3-dihydrobenzo[b]furan
    1904 (Z)-Coriandrin 1234 C12H15ONS2 153
    1905 (Z)-Coridrin 1708 C10H9ONS 191
    1906 (E)-Coridrin 1784 C10H9ONS 191
    1907 2-Methylene-6,6-dimethylcyclohex- 1092 C10H14O 150
    3-ene-1-carbaldehyde
    1908 1-p-Menthan-8-thiol 1196 C10H20S 172
    1909 1-p-Menthen-8-thiol 1279 C10H18S 170
    1910 5,5-Dimethylcyclohex-2-en-1,4- 1002 C8H10O2 138
    dione
    1911 Neoisomenthol 1176 C10H20O 156
    1912 Menth-2-en-1,4-diol 1269 C10H18O2 170
    1913 Carvone hydrate 1388 C10H16O2 168
    1914 Carvone hydrate acetate 1528 C12H18O3 210
    1915 8-Hydroxylinalyl isobutyrate 1588 C14H24O3 240
    1916 Lyral 1637 C13H22O2 210
    1917 Lyral (Isomer) 1625 C13H22O2 210
    1918 2-(4-tert-butylbenzyl)-propione 1501 C14H20O 204
    aldehyde
    1919 Methyl 2-octynoate 1177 C9H14O2 154
    1920 Caparapidiol 1686 C15H28O2 240
    1921 Jaeschkeanadiol 1754 C15H26O2 238
    1922 2,8-Epithio-cis-p-menthane 1242 C10H18S 170
    1923 Gorgona-1,4(15),11-triene 1426 C15H22 202
    1924 Aromadendra-1(10),3-diene 1509 C15H22 202
    1925 8-Hydroxylinalyl 2-methylbutyrate 1688 C15H26O3 254
    1926 trans-Pinane 951 C10H18 138
    1927 4b-Acetoxygymnomitr-3(15)-ene 1739 C17H26O2 262
    1928 1,8-Dimethyl-3-ethyl-2,9- 1344 C11H16O3 196
    dioxabicyclo[3.3.1]non-7-en-6-one
    1929 2,6-Diethyl-2,3-dihydro-4H-pyran- 1221 C9H14O2 154
    4-one
    1930 Frontaline 907 C8H14O2 142
    1931 endo-Brevicomin 1039 C9H16O2 156
    1932 cis-Pinane 963 C10H18 138
    1933 Chalcograne (Isomer 1) 1051 C9H16O 140
    1934 Chalcograne (Isomer 2) 1055 C9H16O 140
    1935 Lineatine 1102 C10H16O2 168
    1936 Methyl n-propyl trisufide 1121 C4H10S3 154
    1937 (E)n-Propyl 1-propenyl disulfide 1063 C6H12S2 148
    1938 Di-n-propyl trisulfide 1302 C6H14S3 182
    1939 Methyl n-propyl disulfide 900 C4H10S2 122
    1940 Di-n-propyl disulfide 1081 C6H14S2 150
    1941 Di-n-propyl tetrasulfide 1558 C6H14S4 214
    1942 5-Pentyl-3,4,5-trimethyl-5H-furan-2- 1474 C12H20O2 196
    one
    1943 Plagiochilline T 1665 C15H20O 216
    1944 Plagiochilline U 1625 C15H22O 218
    1945 5-Methylcyclohex-2-en-1-one 935 C7H10O 110
    1946 3-Ethylcyclohexanone 1020 C8H14O 126
    1947 Methyl 3-ethyl-4-methylpentanoate 1021 C9H18O2 158
    1948 2,4-Diethyloct-1-ene 1106 C12H24 168
    1949 Methyl trans-Dihydrojasmonate 1623 C13H22O3 226
    1950 cis-Methyl dihydrojasmonate 1651 C13H22O3 226
    1951 1,7-Dioxaspiro[5.5]undecane 1108 C9H16O2 156
    1952 (2Z,4E)-Methyl abscisate 2076 C16H22O4 278
    1953 (2Z,4E)-Methyl phaseate 2141 C16H22O5 294
    1954 (2E,4E)-Methyl abscisate 2164 C16H22O4 278
    1955 Pityol 945 C8H16O2 144
    1956 6-Ethyl-2-methyl-2,3-dihydro-4H- 1117 C8H12O2 140
    pyran-2-one
    1957 n-Nonyl acetate 1283 C11H22O2 186
    1958 4-epi-Maaliol 1549 C15H26O 222
    1959 Plagiochiline H 1807 C17H24O3 276
    1960 5-Methyloctahydrofuro [3,2- 1028 C9H16O2 156
    b]oxepine
    1961 Methyl 2-hydroxyhexanoate 993 C7H14O3 146
    1962 Methyl 2-hydroxytetradecanoate 1838 C15H30O3 258
    1963 Seudenol 941 C7H12O 112
    1964 2,8-Dimethyl-1,7- 1121 C11H20O2 184
    dioxaspiro[5.5]undecane (Isomer 1)
    1965 2,8-Dimethyl-1,7- 1189 C11H20O2 184
    dioxaspiro[5.5]undecane (Isomer 2)
    1966 4-Methyl-2-buten-4-olide 869 C5H6O2 98
    1967 Methyl 2-methyltetradecanoate 1758 C16H32O2 256
    1968 Methyl 3-methylpentanoate 840 C7H14O2 130
    1969 Methyl 2-methylundecanoate 1509 C13H26O2 214
    1970 Methyl 2-methyldodecanoate 1550 C14H28O2 228
    1971 Methyl 2-hydroxyisopentanoate 845 C6H12O3 132
    1972 Methyl 2-hydroxypentanoate 894 C6H12O3 132
    1973 4a-Methyloctahydronaphthalen-2- 1369 C11H18O 166
    one
    1974 Methyl madelate 1245 C9H10O3 166
    1975 Methyl 2-hydroxydodecanoate 1627 C13H26O3 230
    1976 1-Phenylethanol 1037 C8H10O 122
    1977 2,3,5-Trimethylvalerolactone 1158 C8H14O2 142
    1978 10-Methyldecalin-2,7-dione 1520 C11H16O2 180
    1979 6-Hexyl-5,6-dihydropyran-2-one 1551 C11H18O2 182
    1980 Methyl 2-methylpentadecanoate 2195 C17H34O2 270
    1981 2,3-Epoxycinnamyl alcohol 1309 C9H10O2 150
    1982 Methyl 2-methylhexadecanoate 1972 C18H36O2 284
  • An exemplary therapeutic compound conforming with any of the disclosed embodiments may comprise for instance a compound including at least two of delta-9-tetrahydrocannabinol or tetrahydrocannabinolic acid, and cannabidiol and optionally at least one of the listed terpenes Still further an exemplary therapeutic compound conforming with any of the disclosed embodiments may comprise for instance a compound including 20 mg of delta-9-tetrahydrocannabinol and 10 mg of cannabidiol preferably administered every δ-8 hours as needed. Still further an exemplary therapeutic compound conforming with any of the disclosed embodiments may comprise for instance a compound including 10 mg of delta-9-tetrahydrocannabinol and 5 mg of cannabidiol preferably administered every δ-8 hours as needed. Still further an exemplary therapeutic compound conforming with any of the disclosed embodiments may comprise for instance a compound including 20 mg of delta-9-tetrahydrocannabinol and 20 mg of cannabidiol preferably administered every δ-8 hours as needed. Still further an exemplary therapeutic compound conforming with any of the disclosed embodiments may comprise for instance a compound including 10 mg of delta-9-tetrahydrocannabinol and 10 mg of cannabidiol preferably administered every δ-8 hours as needed. Still further an exemplary therapeutic compound conforming with any of the disclosed embodiments may comprise for instance a compound including 15 mg of delta-9-tetrahydrocannabinol and 10 mg of cannabidiol preferably administered every δ-8 hours as needed.
  • Further, enumerated embodiments are described below.
  • Embodiment 1. A pharmaceutical composition comprising: (a) tetrahydrocannabinol (THC) and cannabidiol (CBD) in a THC:CBD ratio of from 1:1.5 to 3:1 by weight; and (b) one or more terpenes listed in Table 1.
  • Embodiment 2. The pharmaceutical composition of embodiment 1, wherein the THC:CBD ratio is about: 1:1.5, 1:1.4, 1:1.3, 1:1.2, 1:1.1, 1:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, 2:1, 2.1:1, 2.2:1, 2.3:1, 2.4:1, 2.5:1, 2.6:1, 2.7:1, 2.8:1, 2.9:1, or 3:1.
  • Embodiment 3. The pharmaceutical composition of embodiment 1, wherein the THC:CBD ratio is from 1.5:1 to 2:1.
  • Embodiment 4. The pharmaceutical composition of embodiment 1, wherein the THC:CBD ratio is about 1.5:1.
  • Embodiment 5. The pharmaceutical composition of any one of embodiments 1-4, wherein the pharmaceutical composition comprises: 1-50 mg, 5-40 mg, 7.5-30 mg, 10-20 mg, or 12.5-17.5 mg tetrahydrocannabinol (THC) per dose.
  • Embodiment 6. The pharmaceutical composition of any one of embodiments 1-4, wherein the pharmaceutical composition comprises about: 1 mg, 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg, 17.5 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, or 50 mg tetrahydrocannabinol (THC) per dose.
  • Embodiment 7. The pharmaceutical composition of any one of embodiments 1-4, wherein the pharmaceutical composition comprises about 10-20 mg tetrahydrocannabinol (THC) per dose.
  • Embodiment 8. The pharmaceutical composition of any one of embodiments 1-4, wherein the pharmaceutical composition comprises about 15-20 mg tetrahydrocannabinol (THC) per dose.
  • Embodiment 9. The pharmaceutical composition of any one of embodiments 1-8, wherein the pharmaceutical composition comprises: 1-35 mg, 2.5-30 mg, 5-25 mg, δ-14 mg, 10-12 mg cannabidiol (CBD) per dose.
  • Embodiment 10. The pharmaceutical composition of any one of embodiments 1-8, wherein the pharmaceutical composition comprises about: 1 mg, 1.5 mg, 2 mg, 2.5 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, 17.5 mg, 20 mg, 22.5 mg, 25 mg, 27.5 mg, or 30 mg cannabidiol (CBD) per dose.
  • Embodiment 11. The pharmaceutical composition of any one of embodiments 1-8, wherein the pharmaceutical composition comprises δ-14 mg cannabidiol (CBD).
  • Embodiment 12. The pharmaceutical composition of any one of embodiments 1-8, wherein the pharmaceutical composition comprises 10-12 mg cannabidiol (CBD).
  • Embodiment 13. The pharmaceutical composition of any one of embodiments 1-12, wherein the one or more terpenes comprise β-myrcene, β-caryophyllene, ocimene, α-pinene, α-humulene, linalool, p-cymene, camphene, cis-nerolidol, terpinolene, isopulegol, caryophyllene oxide, δ-limonene, geraniol, guaiol, α-bisabolol, 3-carene, β-pinene, γ-terpinene, or a combination thereof.
  • Embodiment 14. The pharmaceutical composition of any one of embodiments 1-12, wherein the one or more terpenes comprise β-myrcene, β-caryophyllene, ocimene, α-pinene, α-humulene, linalool, p-cymene, and camphene.
  • Embodiment 15. The pharmaceutical composition of any one of embodiments 1-12, wherein the one or more terpenes comprise β-myrcene, β-caryophyllene, ocimene, α-pinene, and α-humulene.
  • Embodiment 16. The pharmaceutical composition of any one of embodiments 1-12, wherein the one or more terpenes comprise β-myrcene, ocimene, cis-nerolidol, terpinolene, isopulegol, caryophyllene oxide, δ-limonene, geraniol, guaiol, and α-bisabolol.
  • Embodiment 17. The pharmaceutical composition of any one of embodiments 1-12, wherein the one or more terpenes comprise β-myrcene, ocimene, cis-nerolidol, terpinolene, isopulegol, caryophyllene oxide, δ-limonene, geraniol, guaiol, α-bisabolol, and 3-carene.
  • Embodiment 18. The pharmaceutical composition of any one of embodiments 1-12, wherein the one or more terpenes comprise β-myrcene, β-caryophyllene, ocimene, α-humulene, linalool, p-cymene, camphene, 3-carene, R-pinene, and γ-terpinene.
  • Embodiment 19. The pharmaceutical composition of any one of embodiments 1-12, wherein the one or more terpenes comprise β-myrcene, β-caryophyllene, ocimene, α-pinene, α-humulene, linalool, p-cymene, camphene, 3-carene, R-pinene, and γ-terpinene.
  • Embodiment 20. The pharmaceutical composition of any one of embodiments 1-19, wherein the one or more terpenes comprise β-myrcene, and wherein the pharmaceutical composition comprises 1-100 mg, 20-80 mg, 30-60 mg, 40-50 mg, 1-10 mg, 1.5-7.5 mg, or 2-5 mg of β-myrcene per dose.
  • Embodiment 21. The pharmaceutical composition of any one of embodiments 1-19, wherein the one or more terpenes comprise β-myrcene, and wherein the pharmaceutical composition comprises about: 1 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.1 mg, 2.2 mg, 2.3 mg, 2.4 mg, 2.5 mg, 2.6 mg, 2.7 mg, 2.8 mg, 2.9 mg, 3 mg, 3.1 mg, 3.2 mg, 3.3 mg, 3.4 mg, 3.5 mg, 3.6 mg, 3.7 mg, 3.8 mg, 3.9 mg, 4 mg, 4.5 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, or 10 mg of β-myrcene per dose.
  • Embodiment 22. The pharmaceutical composition of any one of embodiments 1-19, wherein the one or more terpenes comprise β-myrcene, and wherein the pharmaceutical composition comprises about: 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, or 60 mg of β-myrcene per dose.
  • Embodiment 23. The pharmaceutical composition of any one of embodiments 1-19, wherein the one or more terpenes comprise β-myrcene, and wherein the pharmaceutical composition comprises 1.5-7.5 mg of β-myrcene per dose.
  • Embodiment 24. The pharmaceutical composition of any one of embodiments 1-19, wherein the one or more terpenes comprise β-myrcene, and wherein the pharmaceutical composition comprises 30-60 mg of β-myrcene per dose.
  • Embodiment 25. The pharmaceutical composition of any one of embodiments 1-24, wherein the one or more terpenes comprise β-caryophyllene, and wherein the pharmaceutical composition comprises 1-20 mg, 2-10 mg, 2.5-5 mg, or 3-8 mg of β-caryophyllene per dose.
  • Embodiment 26. The pharmaceutical composition of any one of embodiments 1-24, wherein the one or more terpenes comprise β-caryophyllene, and wherein the pharmaceutical composition comprises about 1 mg, 1.5 mg, 2 mg, 2.25 mg, 2.5 mg, 2.75 mg, 3 mg, 3.1 mg, 3.2 mg, 3.3 mg, 3.4 mg, 3.5 mg, 3.6 mg, 3.7 mg, 3.8 mg, 3.9 mg, 4 mg, 4.25 mg, 4.5 mg, 4.75 mg, 5 mg, 5.5 mg, 6 mg, 6.5 mg, 7 mg, 7.5 mg, 7.6 mg, 8 mg, 9 mg, 10 mg, 12.5 mg, 15 mg, or 20 mg of β-caryophyllene per dose.
  • Embodiment 27. The pharmaceutical composition of any one of embodiments 1-24, wherein the one or more terpenes comprise β-caryophyllene, and wherein the pharmaceutical composition comprises 2.5-5 mg of β-caryophyllene per dose.
  • Embodiment 28. The pharmaceutical composition of any one of embodiments 1-27, wherein the one or more terpenes comprise ocimene, and wherein the pharmaceutical composition comprises 1-20 mg, 2-10 mg, 2.3-4.7 mg, or 3-8 mg of ocimene per dose.
  • Embodiment 29. The pharmaceutical composition of any one of embodiments 1-27, wherein the one or more terpenes comprise ocimene, and wherein the pharmaceutical composition comprises about 1 mg, 1.1 mg, 1.5 mg, 2 mg, 2.1 mg, 2.3 mg, 2.5 mg, 2.75 mg, 3 mg, 3.1 mg, 3.2 mg, 3.3 mg, 3.4 mg, 3.5 mg, 3.6 mg, 3.7 mg, 3.8 mg, 3.9 mg, 4 mg, 4.2 mg, 4.5 mg, 4.7 mg, 5 mg, 5.5 mg, 6 mg, 6.5 mg, 7 mg, 7.5 mg, 7.6 mg, 8 mg, 9 mg, 10 mg, 12.5 mg, 15 mg, or 20 mg of ocimene per dose.
  • Embodiment 30. The pharmaceutical composition of any one of embodiments 1-27, wherein the one or more terpenes comprise ocimene, and wherein the pharmaceutical composition comprises 2.3-4.7 mg of ocimene per dose.
  • Embodiment 31. The pharmaceutical composition of any one of embodiments 1-30, wherein the one or more terpenes comprise α-pinene, and wherein the pharmaceutical composition comprises 0.1-10 mg, 0.5-5 mg, or 1.1-2.1 mg of α-pinene per dose.
  • Embodiment 32. The pharmaceutical composition of any one of embodiments 1-30, wherein the one or more terpenes comprise α-pinene, and wherein the pharmaceutical composition comprises about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.1 mg, 2.2 mg, 2.3 mg, 2.4 mg, 2.5 mg, 2.75 mg, 3 mg, 3.5 mg, 4 mg, 4.5 mg, 5 mg, 7.5 mg, or 10 mg of α-pinene per dose.
  • Embodiment 33. The pharmaceutical composition of any one of embodiments 1-30, wherein the one or more terpenes comprise α-pinene, and wherein the pharmaceutical composition comprises 1.1-2.1 mg of α-pinene per dose.
  • Embodiment 34. The pharmaceutical composition of any one of embodiments 1-33, wherein the one or more terpenes comprise α-humulene, and wherein the pharmaceutical composition comprises 0.1-5 mg, 0.5-3.5 mg, or 0.8-1.6 mg of α-humulene per dose.
  • Embodiment 35. The pharmaceutical composition of any one of embodiments 1-33, wherein the one or more terpenes comprise α-humulene, and wherein the pharmaceutical composition comprises about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.1 mg, 2.2 mg, 2.3 mg, 2.4 mg, 2.5 mg, 2.6 mg, 2.7 mg, 2.8 mg, 2.9 mg, 3 mg, 3.1 mg, 3.2 mg, 3.5 mg, 4 mg, 4.5 mg, or 5 mg of α-humulene per dose.
  • Embodiment 36. The pharmaceutical composition of any one of embodiments 1-33, wherein the one or more terpenes comprise α-humulene, and wherein the pharmaceutical composition comprises 0.8-1.6 mg of α-humulene per dose.
  • Embodiment 37. The pharmaceutical composition of any one of embodiments 1-36, wherein the one or more terpenes comprise linalool, and wherein the pharmaceutical composition comprises 0.1-2 mg, 0.2-1.5 mg, or 0.3-0.9 mg of linalool per dose.
  • Embodiment 38. The pharmaceutical composition of any one of embodiments 1-36, wherein the one or more terpenes comprise linalool, and wherein the pharmaceutical composition comprises about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, or 2 mg of linalool per dose.
  • Embodiment 39. The pharmaceutical composition of any one of embodiments 1-36, wherein the one or more terpenes comprise linalool, and wherein the pharmaceutical composition comprises 0.3-0.9 mg of linalool per dose.
  • Embodiment 40. The pharmaceutical composition of any one of embodiments 1-39, wherein the one or more terpenes comprise p-cymene, and wherein the pharmaceutical composition comprises 0.1-20 mg, 0.25-10 mg, 5-10 mg, or 0.5-0.9 mg of p-cymene per dose.
  • Embodiment 41. The pharmaceutical composition of any one of embodiments 1-39, wherein the one or more terpenes comprise p-cymene, and wherein the pharmaceutical composition comprises about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.5 mg, 3 mg, 4 mg, 5 mg, 5.5 mg, 6 mg, 6.5 mg, 6.75 mg, 7 mg, 7.1 mg, 7.2 mg, 7.3 mg, 7.4 mg, 7.5 mg, 8 mg, 9 mg, 10 mg, 12.5 mg, 15 mg or 20 mg of p-cymene per dose.
  • Embodiment 42. The pharmaceutical composition of any one of embodiments 1-39, wherein the one or more terpenes comprise p-cymene, and wherein the pharmaceutical composition comprises 0.5-0.9 mg of p-cymene per dose.
  • Embodiment 43. The pharmaceutical composition of any one of embodiments 1-42, wherein the one or more terpenes comprise camphene, and wherein the pharmaceutical composition comprises 0.01-2 mg, 0.02-1 mg, 0.03-0.5 mg, or 0.05 to 0.15 mg of camphene per dose.
  • Embodiment 44. The pharmaceutical composition of any one of embodiments 1-42, wherein the one or more terpenes comprise camphene, and wherein the pharmaceutical composition comprises about 0.01 mg, 0.02 mg, 0.03 mg, 0.04 mg, 0.05 mg, 0.06 mg, 0.07 mg, 0.08 mg, 0.09 mg, 0.1 mg, 0.15 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1 mg, 1.25 mg, 1.5 mg, 1.75 mg, or 2 mg of camphene per dose.
  • Embodiment 45. The pharmaceutical composition of any one of embodiments 1-42, wherein the one or more terpenes comprise camphene, and wherein the pharmaceutical composition comprises 0.05-0.15 mg of camphene per dose.
  • Embodiment 46. The pharmaceutical composition of any one of embodiments 1-45, wherein the one or more terpenes comprise cis-nerolidol, and wherein the pharmaceutical composition comprises 0.5-20 mg, 1-10 mg, or 1.5 to 5 mg of cis-nerolidol per dose.
  • Embodiment 47. The pharmaceutical composition of any one of embodiments 1-45, wherein the one or more terpenes comprise cis-nerolidol, and wherein the pharmaceutical composition comprises about 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.25 mg, 2.5 mg, 3 mg, 4 mg, 4.5 mg, 4.8 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg 10 mg, 15 mg, or 20 mg of cis-nerolidol per dose.
  • Embodiment 48. The pharmaceutical composition of any one of embodiments 1-45, wherein the one or more terpenes comprise cis-nerolidol, and wherein the pharmaceutical composition comprises 1.5-5 mg of cis-nerolidol per dose.
  • Embodiment 49. The pharmaceutical composition of any one of embodiments 1-48, wherein the one or more terpenes comprise terpinolene, and wherein the pharmaceutical composition comprises 0.5-10 mg, 1-5 mg, or 1.2 to 3 mg of terpinolene per dose.
  • Embodiment 50. The pharmaceutical composition of any one of embodiments 1-48, wherein the one or more terpenes comprise terpinolene, and wherein the pharmaceutical composition comprises about 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.25 mg, 2.5 mg, 3 mg, 4 mg, 4.5 mg, 4.8 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg 10 mg, 15 mg, or 20 mg of terpinolene per dose.
  • Embodiment 51. The pharmaceutical composition of any one of embodiments 1-48, wherein the one or more terpenes comprise terpinolene, and wherein the pharmaceutical composition comprises 1.2-3 mg of terpinolene per dose.
  • Embodiment 52. The pharmaceutical composition of any one of embodiments 1-51, wherein the one or more terpenes comprise isopulegol, and wherein the pharmaceutical composition comprises 0.1-5 mg, 0.5-3.5 mg, or 0.8 to 2.3 mg of isopulegol per dose.
  • Embodiment 53. The pharmaceutical composition of any one of embodiments 1-51, wherein the one or more terpenes comprise isopulegol, and wherein the pharmaceutical composition comprises about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.3 mg, 2.5 mg, 3 mg, 3.5 mg, 4 mg, 4.5 mg, 4.8 mg, or 5 mg of isopulegol per dose.
  • Embodiment 54. The pharmaceutical composition of any one of embodiments 1-51, wherein the one or more terpenes comprise isopulegol, and wherein the pharmaceutical composition comprises 0.8-2.3 mg of isopulegol per dose.
  • Embodiment 55. The pharmaceutical composition of any one of embodiments 1-54, wherein the one or more terpenes comprise caryophyllene oxide, and wherein the pharmaceutical composition comprises 0.1-5 mg, 0.5-3.5 mg, or 0.8 to 2.2 mg of caryophyllene oxide per dose.
  • Embodiment 56. The pharmaceutical composition of any one of embodiments 1-54, wherein the one or more terpenes comprise caryophyllene oxide, and wherein the pharmaceutical composition comprises about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.2 mg, 2.5 mg, 3 mg, 3.5 mg, 4 mg, 4.5 mg, 4.8 mg, or 5 mg of caryophyllene oxide per dose.
  • Embodiment 57. The pharmaceutical composition of any one of embodiments 1-54, wherein the one or more terpenes comprise caryophyllene oxide, and wherein the pharmaceutical composition comprises 0.8-2.2 mg of caryophyllene oxide per dose.
  • Embodiment 58. The pharmaceutical composition of any one of embodiments 1-57, wherein the one or more terpenes comprise δ-limonene, and wherein the pharmaceutical composition comprises 0.1-5 mg, 0.5-3.5 mg, or 0.8 to 1.6 mg of δ-limonene oxide per dose.
  • Embodiment 59. The pharmaceutical composition of any one of embodiments 1-57, wherein the one or more terpenes comprise δ-limonene, and wherein the pharmaceutical composition comprises about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.2 mg, 2.5 mg, 3 mg, 3.5 mg, 4 mg, 4.5 mg, 4.8 mg, or 5 mg of δ-limonene per dose.
  • Embodiment 60. The pharmaceutical composition of any one of embodiments 1-57, wherein the one or more terpenes comprise δ-limonene, and wherein the pharmaceutical composition comprises 0.8-1.6 mg of δ-limonene per dose.
  • Embodiment 61. The pharmaceutical composition of any one of embodiments 1-60, wherein the one or more terpenes comprise geraniol, and wherein the pharmaceutical composition comprises 0.1-3 mg, 0.2-1.5 mg, or 0.4 to 0.9 mg of geraniol per dose.
  • Embodiment 62. The pharmaceutical composition of any one of embodiments 1-60, wherein the one or more terpenes comprise geraniol, and wherein the pharmaceutical composition comprises about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.2 mg, 2.5 mg, or 3 mg of geraniol per dose.
  • Embodiment 63. The pharmaceutical composition of any one of embodiments 1-60, wherein the one or more terpenes comprise geraniol, and wherein the pharmaceutical composition comprises 0.4-0.9 mg of geraniol per dose.
  • Embodiment 64. The pharmaceutical composition of any one of embodiments 1-63, wherein the one or more terpenes comprise guaiol, and wherein the pharmaceutical composition comprises 0.1-5 mg, 0.2-3.5 mg, or 0.4 to 3.2 mg of guaiol per dose.
  • Embodiment 65. The pharmaceutical composition of any one of embodiments 1-63, wherein the one or more terpenes comprise guaiol, and wherein the pharmaceutical composition comprises about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.2 mg, 2.4, 2.5 mg, 2.75, 3 mg, 3.2 mg, 3.5 mg, 4 mg, 4.5 mg, or 5 mg of guaiol per dose.
  • Embodiment 66. The pharmaceutical composition of any one of embodiments 1-63, wherein the one or more terpenes comprise guaiol, and wherein the pharmaceutical composition comprises 0.4-3.2 mg of guaiol per dose.
  • Embodiment 67. The pharmaceutical composition of any one of embodiments 1-66, wherein the one or more terpenes comprise α-bisobolol, and wherein the pharmaceutical composition comprises 0.1-3 mg, 0.2-1.5 mg, or 0.3 to 0.7 mg of α-bisobolol per dose.
  • Embodiment 68. The pharmaceutical composition of any one of embodiments 1-66, wherein the one or more terpenes comprise α-bisobolol, and wherein the pharmaceutical composition comprises about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.2 mg, 2.5 mg, or 3 mg of α-bisobolol per dose.
  • Embodiment 69. The pharmaceutical composition of any one of embodiments 1-66, wherein the one or more terpenes comprise α-bisobolol, and wherein the pharmaceutical composition comprises 0.3-0.7 mg of α-bisobolol per dose.
  • Embodiment 70. The pharmaceutical composition of any one of embodiments 1-69, wherein the one or more terpenes comprise 3-carene, and wherein the pharmaceutical composition comprises 0.1-3 mg, 0.2-1.5 mg, or 0.4 to 0.9 mg of 3-carene per dose.
  • Embodiment 71. The pharmaceutical composition of any one of embodiments 1-69, wherein the one or more terpenes comprise 3-carene, and wherein the pharmaceutical composition comprises about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.2 mg, 2.5 mg, or 3 mg of 3-carene per dose.
  • Embodiment 72. The pharmaceutical composition of any one of embodiments 1-69, wherein the one or more terpenes comprise 3-carene, and wherein the pharmaceutical composition comprises 0.4-0.9 mg of 3-carene per dose.
  • Embodiment 73. The pharmaceutical composition of any one of embodiments 1-72, wherein the one or more terpenes comprise β-pinene, and wherein the pharmaceutical composition comprises 0.1-5 mg, 0.3-3 mg, or 0.6 to 2.0 mg of β-pinene per dose.
  • Embodiment 74. The pharmaceutical composition of any one of embodiments 1-72, wherein the one or more terpenes comprise β-pinene, and wherein the pharmaceutical composition comprises about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, 2 mg, 2.2 mg, 2.4, 2.5 mg, 2.75, 3 mg, 3.2 mg, 3.5 mg, 4 mg, 4.5 mg, or 5 mg of β-pinene per dose.
  • Embodiment 75. The pharmaceutical composition of any one of embodiments 1-72, wherein the one or more terpenes comprise β-pinene, and wherein the pharmaceutical composition comprises 0.6-2.0 mg of β-pinene per dose.
  • Embodiment 76. The pharmaceutical composition of any one of embodiments 1-75, wherein the one or more terpenes comprise γ-terpinene, and wherein the pharmaceutical composition comprises 0.05-1.6 mg, 0.1-0.8 mg, or 0.2 to 0.4 mg of γ-terpinene per dose.
  • Embodiment 77. The pharmaceutical composition of any one of embodiments 1-75, wherein the one or more terpenes comprise γ-terpinene, and wherein the pharmaceutical composition comprises about 0.05 mg, 0.06 mg, 0.07 mg, 0.08 mg, 0.09 mg, 0.1 mg, 0.11 mg, 0.12 mg, 0.13 mg, 0.14 mg, 0.15 mg, 0.16 mg, 0.17 mg, 0.18 mg, 0.19 mg, 0.20 mg, 0.21 mg, 0.22 mg, 0.23 mg, 0.24 mg, 0.25 mg, 0.26 mg, 0.27 mg, 0.28 mg, 0.29 mg, 0.3 mg, 0.31 mg, 0.32 mg, 0.33 mg, 0.34 mg, 0.35 mg, 0.36 mg, 0.37 mg, 0.38 mg, 0.39 mg, 0.4 mg, 0.45 mg, 0.5 mg, 0.55 mg, 0.6 mg, 0.75 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, or 1.6 mg of γ-terpinene per dose.
  • Embodiment 78. The pharmaceutical composition of any one of embodiments 1-75, wherein the one or more terpenes comprise γ-terpinene, and wherein the pharmaceutical composition comprises 0.2-0.4 mg of γ-terpinene per dose.
  • Embodiment 79. The pharmaceutical composition of any one of embodiments 1-78, wherein the one or more terpenes comprise β-myrcene, β-caryophyllene, ocimene, α-pinene, α-humulene, or a combination thereof, and wherein the pharmaceutical composition comprises about 30-60 mg of the β-mycene, about 2.5-5 mg of the β-caryophyllene, about 2.3-4.7 mg of the ocimene, about 1.1-2.1 mg of the α-pinene, about 0.8-1.6 mg of the α-humulene, or a combination thereof per dose.
  • Embodiment 80. The pharmaceutical composition of any one of embodiments 1-78, wherein the one or more terpenes comprise β-myrcene, β-caryophyllene, ocimene, α-pinene, and α-humulene; and wherein the pharmaceutical composition comprises about 30-60 mg of the β-mycene, about 2.5-5 mg of the β-caryophyllene, about 2.3-4.7 mg of the ocimene, about 1.1-2.1 mg of the α-pinene, and about 0.8-1.6 mg of the α-humulene per dose.
  • Embodiment 81. The pharmaceutical composition of any one of embodiments 1-80, wherein the pharmaceutical composition is formulated as a liquid, a pill, a gel capsule, a vaporizable liquid, a vaporizable solid, a transdermal ointment or salve, or a transdermal patch.
  • Embodiment 82. The pharmaceutical composition of any one of embodiments 1-80, wherein the pharmaceutical composition is formulated as a liquid.
  • Embodiment 83. The pharmaceutical composition of embodiment 82, wherein the liquid comprises citric acid, blue agave, glycerine, one or more lorann oils, food coloring, or a combination thereof.
  • Embodiment 84. The pharmaceutical composition of embodiment 82, wherein the liquid comprises: (a) about 1% to 7% w/w citric acid; (b) about 40% to 49% w/w blue agave; (c) about 40% to 49% w/w glycerin; (d) about 0.1% to 1.5% w/w lorann oils; (e) about 0.01 to 0.4% food coloring; (f) or a combination thereof.
  • Embodiment 85. The pharmaceutical composition of embodiment 82, wherein the liquid comprises: (a) about 1% to 7% w/w citric acid; (b) about 40% to 49% w/w blue agave; (c) about 40% to 49% w/w glycerin; (d) about 0.1% to 1.5% w/w lorann oils; and (e) about 0.01 to 0.4% food coloring.
  • Embodiment 86. The pharmaceutical composition of embodiment 82, wherein the liquid comprises: (a) about 3-5% w/w citric acid; (b) about 45-49% w/w blue agave; (c) about 45-49% w/w glycerin; (d) about 0.7-0.9% w/w lorann oils; and (e) about 0.1-0.3% food coloring.
  • Embodiment 87. The pharmaceutical composition of any one of embodiments 1-86, for use in the treatment of opioid addiction.
  • Embodiment 88. The pharmaceutical composition of any one of embodiments 1-86, for use in the treatment of pain.
  • Embodiment 89. The pharmaceutical composition of any one of embodiments 1-86, for use in the treatment of chemotherapy-induced nausea and vomiting.
  • Embodiment 90. A method of treating opioid addition, the method comprising administering an effective amount of a pharmaceutical composition comprising one or more cannabinoids to a subject in need thereof.
  • Embodiment 91. The method of embodiment 90, wherein the pharmaceutical composition is the pharmaceutical composition of any one of embodiments 1-86.
  • Embodiment 92. The method of embodiment 90 or 91, wherein the pharmaceutical composition is administered every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours.
  • Embodiment 93. The method of embodiment 90 or 91, wherein the pharmaceutical composition is administered every 6, 8 or 12 hours.
  • Embodiment 94. The method of any one of embodiment 90-93, wherein the subjects opioid use decreases by at least 50% within 5 weeks of beginning treatment as determined by morphine equivalency of opioids used.
  • Example 1 —Exemplary Formulation Preparation
  • This example details the production of an exemplary cannabinoid formulation that can be used in the methods disclosed herein.
  • Briefly, 400 g citric acid, 5000 g blue agave, and 5000 g glycerin are mixed and heated to 150° C. Separately, 300 g ethanol is heated and mixed with THC oil and CBD isolate until complete dissolution. Then, both mixtures are combined, flavoring (80 g Lorann Oils, e.g., watermellon, cherry) and coloring (20 g food coloring) are added, and the resulting mixture is sonicated until ingredients are thoroughly incorporated.
  • The final product is aliquoted to bottles, each containing about 5.5 oz. A single dose is about 12 mL.
  • The final product can contain, for example, about 15-20 mg THC and about 10-12 mg CBD per dose. The final product can also contain terpenes; for example, 30-60 mg 0-myrcene (e.g., about 45 mg), 2.5-5 mg β-caryophyllene (e.g., about 3.7 mg), 2.3-4.7 mg ocimene (e.g., about 3.5), 1.1-2.1 mg α-pinene (e.g., about 1.6), 0.8-1.6 mg α-humulene (e.g, about 1.2 mg), or a combination thereof. Table 2 contains an exemplary recipe.
  • TABLE 2
    Exemplary formulation recipe
    Batch Size: 10,000 g
    16 g formulation = 12 mL volume = 1 dose
    Percent
    Amount by
    Component Added Weight mg/g mg/dose
    Carriers/Excipients
    Citric Acid 393.27 g 3.933%
    Blue Agave 4729.13 g 47.291% 
    Glycerine 4729.13 g 47.291% 
    Flavor: Lorann 78.65 g 0.787%
    Oils
    Food Coloring 19.66 g 0.197%
    Cannabinoids
    THC 9.38 g 0.094% 0.9375 mg/g 15 mg/dose
    CBD 6.25 g 0.063% 0.625 mg/g 10 mg/dose
    Terpenes
    β-myrcene 28.13 g 0.281% 2.8125 mg/g 45 mg/dose
    β- 2.31 g 0.023% 0.23125 mg/g 3.7 mg/dose
    Caryophyllene
    Ocimene 2.19 g 0.022% 0.21875 mg/g 3.5 mg/dose
    α-pinene 1.00 g 0.010% 0.1 mg/g 1.6 mg/dose
    α-humulene 0.75 g 0.008% 0.075 mg/g 1.2 mg/dose
  • Example 2
  • Over the last 150 years the perceived and reported medicinal effects or benefits associated with the consumption of products derived from the cannabis plant have fluctuated as much as the most volatile stock market period in history. Periodically, the benefits have been held out to be Olympian in nature, virtually a cure all for all conditions while at other times use of the cannabis has been associated with “reefer madness”; including suicidal ideation, sexual promiscuity, and in general uncontrolled impulses. The truth, as usual lies somewhere in between. Add in a dose of world politics and posturing; difficulty in conducting trials; an error in taxonomy; the radically different effect ascribed to the two main components of the plant, Delta-9 tetrahydrocannabinol (THC) and Cannabidiol (CBD) consumed in a variety of ways; a less than clear understanding of the metabolism of the compounds and the endocannabinoid system; and the inability to link a specific plant profile to a specific outcome have all made it even more difficult in separating the flower from the trim, as it pertains to cannabis Sativa and its medicinal effects.
  • For the purposes of this forum the historic marketing of cannabis and its by-products will be left to an excellent reference as will references to reefer madness type publications. Regarding world and US politics, our present-day situation, for the most part, is governed nationally by the Nixon administration ignoring the recommendations of the National Commission of Marihuana and Drug Abuse (The Schafer Commission) and its appendix both published in 1972, which overall called for decriminalization of personal possession and use of cannabis. Even this report was not without controversy. To paraphrase a report issued by the Committee on Public Health of the New York Academy of Medicine, it recommended that a government agency investigate the feasibility of control and distribution of marihuana through a government agency, while a New England Journal editorial suggested that legalization offered the best promise for effective control of marihuana. Nahas and Greenwood published a detailed rebuttal to the Shafer Commission report and ultimately the administration ignored the Commission's recommendations. Currently 28 states, the District of Columbia and a few of the over 500 recognized Indian tribal nations have passed laws regulating the sale of cannabis either for medical or both medical and recreational use and the laws enacted by each of these government(s) or their legislation are at odds with federal statute. The recent rescinding of the Cole memorandum by Attorney General Sessions has added fuel to the fires of confusion which unfortunately will not be solved here but all should be left with the warning of “buyer beware”.
  • Now onto the science. Like staging systems for each cancer, we can all argue the merits of the specifics defining each stage, but none would argue against the need for uniformity. For without it, discussion of results and therefore evaluation of new treatments would be rendered impossible. Cannabis, was taxonomically divided into three species in the 1970s; C. indica, C. sativa, and C. ruderalis. Adding to the confusion, yet ultimately clarifying was the work of McPartland wherein he proved on a genetic basis that these were all the same species, just different subspecies. More importantly he found that C. sativa originated in India and should have been classified as C. indica; C. indica originated in Afghanistan and should have been identified as C. afghanica; and C. ruderalis is most properly classified as C. sativa. Until this nomenclature is standardized comparing research results will be near impossible.
  • Since Mechooulam's group identified and synthesized both cannabidiol (CBD) and delta-9 tetrahydrocannabinol (THC) the psychoactive component in the cannabis plant there have been over 60 phytocannabinoids the identified in addition to approximately 400 other components of the cannabis plant including a large number of terpenes that account for the associated aroma and may contribute to the entourage effects of cannabis. Research efforts have logically been based upon our understanding of the cannabinoid receptors so far identified throughout the body, but particularly in the brain and metabolism via the cytochrome P450 pathways. Left to further study is the molecular basis for the therapeutic effect of associated with cannabidiol (CBD) as it has little affinity for the CB1 and CB2 receptors. Of most importance at this time has been the identification of CBD acting as a negative allosteric modulator thereby changing the shape of the CB1 receptor and thus dampens the psychoactive effect associated with the consumption of THC when taken in combination with CBD.
  • Much of our collective knowledge regarding the clinical effects of cannibinoids arises from case reports and observational and retrospective studies. There are few prospective randomized trials reported. Many that pertain to clinical oncology involve the use of dronabinol for the relief of chemotherapy-induced nausea and vomiting and pain. May and Giode have thoroughly reviewed much of this literature. Dronabinol has offered little relief over available anti-emetic regimens. Additional prospective studies have been conducted using oromucosal nabiximols (THC:CBD of 1:1) for intractable spasticity in patients with multiple sclerosis (MS) and those results led to the FDA ultimately granting GW Pharmaceuticals (London UK, Carlsbad CA) approval for this indication. Trials using the same product, designed to determine its effectiveness in cancer-associated pain, was not found to be better than placebo. Maccarrone et al have reviewed results of trials involving oromucosal nabiximols. Russo similarly has provided an excellent review on the matter of trial design and other controversies associated with research in this area, including issues involving clinical trial approval and design. Highlighted by Russo are the difficulties encountered when attempting to undertake research involving cannabis, in particular the need to either use cannabis provided exclusively by the University of Mississippi or apply to cultivate and supply your study drug.
  • In Nevada, efforts to conduct federally-approved research undertaken with the intent of filing a new drug application a has been thwarted as the Institutional Review Board (IRB) at the University Medical Center (UMC) requires DEA assurance before considering any protocol containing cannabis in a treatment arm, yet to obtain federal permission one needs IRB approval of the study of concern.
  • Addressing the opiate crisis in this country has led to a number of studies being conducted using cannabis-based therapy as an alternative means of managing chronic and cancer-related pain. Despite Nabiximols not appearing to be statistically superior when compared to placebo in controlling pain in cancer patients, there are other randomized placebo controlled trials demonstrating the efficacy of using cannabis for pain control. There is also significant evidence that a cannabis-opioid interaction exists that results in improved pain control. All of the studies to date have either used pain scales or patient interview results to determine the success or failure of the cannabis intervention. Given the increasing availability of legal cannabis, there will be fewer opportunities to study a cannabis naïve population use as it is clear from the work of Bachhuber et al. that patients are self-treating with cannabis in order to reduce if not eliminate their dependence on narcotics. This is reflected by the 24% reduction in opiate-related deaths in states with legalized medical marijuana programs as compared to those without.
  • We, a group of physicians in Nevada, are licensed to cultivate, produce and sell cannabis-related products and have recently undertaken a randomized, placebo controlled study using a guava-based syrup with a THC:CBD ratio of about 2:1 and a placebo containing only the flavored guava-based syrup. As a proof of concept 25 patients with a history of at least 3 years of chronic opiate use were enrolled in a single arm study with the endpoint being a 30% reduction of opiate intake determined by weekly pill count.
  • The population of subjects in this study included 14 women and 11 men. The average age of participants was about 55 years old, with the youngest being 21 and the oldest being 77. The median age was about 58 years old. According to their medical histories, 4 participants had a history of gynecologic or breast cancer; 11 participants have had spine surgery; 5 participants have had a hysterectomy; 4 participants reported hypertension; 2 participants reported coronary artery disease, 2 participants had diabetes; 11 participants used tobacco; 6 participants used alcohol; and 3 participants reported drug abuse.
  • A morphine equivalent calculation was adopted for this study to account for the varying opiates used by the study participants. Hydrocodone alone was used by 9 participants; hydrocodone plus morphine sulfate was used by 1 participant; hydromorphone alone was used by 2 participants; hydromorphone plus methadone was used by 1 participant; oxycodone alone was used by 6 participants; oxycodone plus methadone was used by 1 participant; oxycodone plus morphine sulfate was used by 2 participants; and Percocet was used by 3 participants.
  • 23 of the 25 patients reduced their opiate intake by greater than 50%. The average weekly pill count is charted in FIG. 1 a with regression analysis shown in FIG. 1 b . The average weekly pill counts after conversion to morphine equivalents is shown in FIG. 2 a with regression analysis shown in FIG. 2 b . These results provide an objective basis to evaluate the potential of cannabis to replace to reduce the opiate consumption across the US. We have also opened a trial to evaluate the effectiveness of this syrup with some slight modifications in the terpene profile, in controlling chemotherapy-induced nausea and vomiting (CINV).
  • References, each of which is incorporated by reference in its entirety:
      • Mills M. Moguls and Mexicans: The American history of cannabis legalization. The New Econom Mar. 27, 2015. theneweconomy.com.
      • National Commission on Marihuana and Drug Abuse: Marihuana: A Signal of Misunderstanding: First Report of the National Commission on Marihuana and Drug Abuse. Washington D.C., Govt. Print. Off. 1972.
      • National Commission on Marihuana and Drug Abuse: Marihuana: A Signal of Misunderstanding: Technical papers, Appendix, vols. 1 and 2. Washington D.C., Govt. Print. Off. 1972.
      • Wechsler H. Marihuana, alcohol and public policy. New Eng. J. Med. 287:516-17, 1972
      • Nahas G G, Greenwood A. The first report of the National Commission on marihuana (1972): signal of misunderstanding or exercise in ambiguity. Bull N Y Acad Med. 1974 Jan;50(1):55-75.
      • McPartland J M. “Cannabis sativa and Cannabis indica versus “Sativa” and “Indica”.” In Cannabis sativa L.—Botany and Biotechnology, edited by Chandra S, Lata H and ElSohly M A, pp 101-121. Switzerland: Springer International Publishing, 2017.
      • Micholaum R and Shvo Y. Hasish. I. The structure of cannabidiol.Tetrahedron. 1963 Dec; 19(12): 2073-8
      • Gaoni Y and Micholaum R. Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish.J. Am. Chem. Soc., 1964, 86 (8), pp 1646-1647.
      • Howlett A C1, Barth F, Bonner T I, Cabral G, Casellas P, Devane W A, Felder C C, Herkenham M, Mackie K, Martin B R, Mechoulam R, Pertwee R G. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev. 2002 Jun;54(2):161-202.
      • Breivogel C S1, Childers S R. The functional neuroanatomy of brain cannabinoid receptors. Neurobiol Dis. 1998 December;5(6 Pt B):417-31
      • Russo E B. Taming THC; potential cannabis synergy and phytocannabinoid=terpenoid entourage effects. Br J Pharmacol. 2011 August; 163 (7):1344-1364.
      • Lapairie R B, Bagher, A M, Kelly, M E Denovan-Wright, E M. Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. Br J Pharmacol. 2015 October; 172(20): 4790-4805.
      • May M B and Glode A E. Dronabinol for chemotherapy-induced nausea and vomiting unresponsive to anti-emetics. Cancer Manag Res. 2016; 8: 49-55.
      • Maccarrone M, Maldanado R, Casas M, Henze T, and Centonze D. Cannabinoids therapeutic use: what is our current understanding following the introduction of THC, THC:CBD oromucosal spray and others? Expert Review of Clinical Pharmacology. 2017; 10: 443-55.
      • Russo E B. Current Therapeutic Cannabis Controversies and Clinical Trial Design Issues. Front Pharmacol. 2016; 7: 309-339.
      • Lichtman A H, Lux E A, McQuade R, Rossetti s, Sanchez R, Sun W. Wright S, Kornyeyeva E, Fallon M T. Results of a double-blind, randomized, placebo-controlled study of Nabiximols oromucosal spray as an adjunctive therapy in advanced cancer patients with chronic uncontrolled pain.nJ Pain Symptom Manage. 2018; 55: 179-188.
      • Abrams D I, Couey P, Shader S B, Kelly M E, Benowitz N I. Cannabinoid-opioid Interaction in chronic pain. Clin. Pharmacol. Ther. 2011; 90; 844-851.
      • Miller G. Pot and Pain. Hints are emerging that cannabis could be an alternative to opioid painkillers. Science. 2016: 354; 566-568
      • Whiting P F, Wolff R E, Deshpande S, Di Niso M, Duffy S, Hemandez A V, Keurentjes J C, Lang S, Misso K, Rider s, Schmidkofer S, Westwood M, Kleijnen J. Cannabinoids for Medical Use: A systematic review and meta-analysis. JAMA. 2015; 313; 2456-2473.
      • Bachhuber M A, Saloner B, Cunningham C O, Barry C L. Medicinal cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010. JAMA Intern. Med. 2014 174; 1668-1673.
    EXAMPLE 3 a Phase III Double-Blind, Randomized, Placebo Controlled (with Crossover) Trial of Medical Marijuana Versus Placebo for the Reduction of Opiate Consumption in Patients with Chronic Pain
  • Arm I: Placebo Arm II: THC/CBD (strain specific)
    If no improvement If no improvement
    Double the Dose Double the Dose
    If no improvement, Cross-over to If no improvement, Cross-over to
    Arm II Arm I
  • Objectives
  • Primary Objective: To determine if the number of patients consuming opiates for chronic pain treate d with medicinal cannabis (15-20 mg THC/10-12 mg CBD-strain specific) in an agave-based syrup that are able to eliminate their opiate consumption is not reduced by 300% when compared to an identical agave-based syrup without cannabis.
  • Secondary Objective: To determine the incidence of adverse events associated with both regimens. Common Terminology for Adverse Events (CTAE ver. 4) will be used to scale adverse events.
  • Background and Rationale
  • The available literature on the medicinal effects of cannabis is sparse and for the most part lacks critical aspects of study design including prospective design and randomization. The reasons for this are varied, but primarily they are based on the fact that cannabis remains a schedule 1 drug and its production and ingestion are against federal law. Most studies have evaluated synthetics, nabilone or dronabinol, with few evaluating THC derived from plant. Internationally, over 30 countries have approved its use either recreationally or medicinally. Some countries such as Paraguay and Chile have legalized cultivation and production of cannabis products. Over half of the states and the District of Columbia have legalized the use of cannabis medicinally and some have approved its use recreationally. In the last few years, research into the underlying neurophysiology associated with cannabis has led to an increased understanding of the different active components and the biochemical pathways responsible for the associated therapeutic effects. The constituents seemingly responsible for the claimed medicinal effects of the cannabis plant can include delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD).
  • The purported beneficial medicinal effects associated with cannabis ingestion are quite diverse. Of the claims made, the most studied are in patients with multiple sclerosis, where a beneficial effect on muscle spasticity and pain are well-documented, but not necessarily as consistently as one might like. Cannabis can also be effective in treating seizures, anorexia, chronic pain, and nausea and vomiting that is associated with chemotherapy. Cannabidiols may also have a therapeutic effect of inflammation, diabetes, cancer, and neurodegenerative diseases. On the other hand THC ingestion has been associated with less than desirable side effects such as agitation; panic disorder; depression and even psychosis.
  • Perhaps as importantly, the political landscape is changing as rapidly as is the understanding of the underlying mechanisms of action associated with cannabis. Indications of this are the increasing number of states that have legalized the medicinal use of cannabis and the call by some states, such as Nevada, to undertake research to evaluate the clinical benefits associated with the use of cannabis.
  • The opiate epidemic continues to be associated with over 100 deaths daily in the United States. Couple this with the estimated total annual cost of pain-related health of approximately $600 billion and perhaps this figure is even higher for the nations in European Union (EU) and therein is born the impetus to evaluate virtually any therapy that may thwart these related problems. This estimate includes the actual costs related to the medical care as well as the economic losses which contribute to approximately one-half of these costs. Economic losses include claimed disability, loss of productivity and lost wages. Medical care including physician time, hospitalization, surgical procedures, diagnostic testing and prescription drugs all contribute to the costs associated with the treatment of pain, as well the costs associated with the adverse effects associated with their utilization. Unfortunately, one of the adverse effects associated with prescription painkillers is death. Overdose deaths secondary to prescription opioids were five times higher in 2016 than 2000 and sales of these prescription drugs have quadrupled. That being said, the number of deaths dues to prescription opioids has remained relative stable at approximately 14,000 to 16,000 deaths per year. Much of the increase in mortality related to opioid consumption is due the rapid rise in those associated with the use of synthetic opioids. Of importance is the fact that in state with either medical marijuana or both medical and retail marijuana programs in place there was a 24.8% lower mean annual opiod overdose mortality rate (95% CI, −37.5% to −9.5%: P=0.003) compared with states without medical marijuana laws.
  • Addressing the opiate crisis in this country has led to a number of studies being conducted using cannabis-based therapy as an alternative means of managing chronic and cancer-related pain. Despite Nabiximols not appearing to be superior when compared to placebo in controlling pain in cancer patients, cannabis may have efficacy for pain control. A cannabis-opioid interaction may also result in improved pain control.
  • Cannabis contains at least 63 cannabinoids but two are best understood studied. The first, delta-9 tetrahydrocannabinol (THC), is thought to be responsible for the psychoactive effects that are widely associated with cannabis. The other main active component, cannabidiol (CBD), has no known psychoactive effect associated with its consumption but is thought to possibly provide anti-neoplastic, analgesic and antineuroleptic effects. Even though both cannabinoids are present in every plant, the interactions with the cerebral endocannabinoid receptor system are quite different. CBD binds as an antagonist to the cannabinoid receptor CB1 but the bond between THC and the same receptor is at least 100 times stronger. CBD also antagonizes the action on the cannabinoid G protein-coupled receptor GPR55, which is thought to be responsible the different neuromodulatory actions as the CB1 receptor. Claims of the subjective effects associated with cannabis ingestion include improvement in mood; relaxation; and increased sensitivity. On the other hand THC ingestion has been associated with less than desirable adverse effects such as agitation; panic disorder; depression and even psychosis.
  • Cannabinoids can have an effect on serotonergic systems, including increasing cerebral production of 5-hydroxytryptamine (5-HT), serotonin while decreasing its uptake at the synapse level. THC may also have dopaminergic antagonistic actions which may contribute to its beneficial profile regarding pain control.
  • Other phytocannabinoids such as cannabichromene (CBC), cannabigerol (CBG) as well as a number of terpenoids may contribute its analgesic effect. CBD, cannabinol (CBN),CBC and CBG can have anti-inflammatory and analgesic effects over and beyond that associated with THC. B-caryophyllene may be a selective CB2 agonist and other terpenes such as linalool and α-Pinene may have analgesic and anti-inflamatory effects respectively. Myrcene on the other hand may have analgesic effects mediated through an opioid-like action. This may lead to another avenue as to how cannabis and it component parts may prevent opiate withdrawal and allow for the use of lesser amounts of opioids while preventing the development of tolerance. Used in combination with opioid pain medications, cannabis can lower opioid side effects, cravings, and withdrawal severity, as well as enhance the analgesic effects of opioids, thereby allowing for lower doses and less risk of overdose.
  • All of the studies to date have either used pain scales or patient interview results to determine the success or failure of the cannabis intervention.
  • We have recently undertaken a phase II feasibility trial using a guava-based syrup with a THC:CBD ratio of 1.5: 1 to 2:1 derived from a specific cannabis plant with a unique profile of other phytocannabinoids such as CBC, CBN, and CBG as well as a number of terpenoids which likely contribute to its analgesic effect. Each dose of syrup contained 15-20 mg of THC and 10-12 mg of CBD as well as a unique profile associated with one specifically bred cannabis plant. A proof of concept trial of 25 patients with a history of at least 3 years of chronic opiate use were enrolled in a single arm study with the target for success being a 30% reduction of opiate intake determined by weekly pill count. Using a morphine equivalent conversion of all of the various opiates consumed by the study population it was determined that there was a reduction in opiate consumption of approximately 75% and 8/25 patients (40%) were able to replace their prescription opiates with the agave-based THC-CBD syrup. This provides an objective basis to evaluate the potential of cannabis to reduce if not eliminate a significant amount of the opiate consumption across the US. As explained above the actions of THC, CBD, and associated terpenes are potentially complementary and the recent feasibility trial provides substantial evidence of potential benefit of using them together for patients with chronic pain.
  • That being said another important consideration in administering cannabis to patients is the potential drug-to-drug interactions and adverse effects associated with its use and potential withdrawal. THC is metabolized via the Cytochrome P450 pathway and more specifically it is thought that the CYP2C9 enzyme is responsible for the first pass metabolism of THC. The CYP3A4 enzyme may also have a role in its metabolism. Coumadin effect on prothrombin time (PT) is significantly enhanced by the use of THC/CBD. Theophylline levels may be adversely affected. There have been reported adverse events when cannabis is used with sildenafil, including a myocardial infarction. Since THC is a CNS depressant its use with alcohol, barbiturates, antihistamines, narcotics, and BZD, theoretically could amplify the effects of both drugs. It should be noted there has not been any clinical trial documenting these interactions. Similarly, adverse events need to be carefully documented. In this context cannabinoid receptors are not located in the brainstem as are opioid receptors and therefore do not have the associated risk of respiratory depression and death. Adverse effects including, but not limited to tachycardia and hypotension, anxiety and nervousness, hyperactivity, muscle relaxation, decreased bowel motility, and bronchodilatation have been documented.
  • The addictive potential of cannabinoids is thought to be lower than opiates and its derivatives as well as other frequently abused substances. Interestingly, as cannabinoids are stored in adipose, excretion takes place over a relatively long-time thus preventing precipitous declines in the plasma concentration and potentially explaining the lack of acute withdrawal symptoms associated with the cessation of cannabis use. Nevertheless, there have been documented symptoms associated with withdrawal including, but not limited to, nausea and vomiting, increased activity, nervousness, irritability, insomnia, and vasomotor symptoms.
  • This overall safety profile of the cannabinoids made them an excellent candidate to be studied as an opiate substitute. A recently completed pilot study demonstrated in 25 patients, a 75% reduction in opiate ingestion over a 4-5 week period, with 8/25 patients completely discontinuing their opiate use. The same formulation used in that study will be studied here.
  • Inclusion of Women and Minorities
  • No potential subject will be excluded from participating in this or any study solely on the basis of ethnic origin or socioeconomic status. Every attempt will be made to enter all eligible patients into this protocol and therefore address the study objectives in a patient population representative of the entire population currently consuming opiates for over three years.
  • PATIENT ELIGIBILITY AND EXCLUSIONS
  • Eligible Patients Criteria
      • 1) Patients currently consuming opiates chronically for a minimum of 3 years.
      • 2) Patients who can read understand and write English or have a translator available to do so.
      • 3) Patients who are able to complete the assessments.
      • 4) Patients who are able to comply with treatment regimen and be seen on a weekly basis at the study site to have their medications counted and an assessment completed.
      • 5) Patient must hold a valid Nevada Medical Marijuana Card or be qualified by reciprocity as defined by Nevada Statute.
  • Ineligible Patients Criteria
      • 1) Patients who, in the opinion of their physician, have any condition that may contradict potential withdrawal symptoms associated potential reduction of opiate ingestion.
      • 2) Patients known to have had a hypersensitivity reaction to any of the drugs to be received as part of this trial.
      • 3) Patients currently taking warfarin or similar products.
      • 4) Patients taking Tadalafil (Cialis T M), Sildenafil (Viagra), or Theophylline.
      • 5) Pregnant patients or patients on oral contraceptives who are not willing to use another form of back up birth control in addition to the pill.
      • 6) Patients who have used cannabis within the last one month.
  • Study Modalities
  • Tetrahydrocannabinol: Cannabidiol (THC:CBD) agave based syrup (20 mg THC/10 mg CBD) vs control agave-based syrup.
  • Each bottle will contain either 150-200 mg:100-120 mg (THC:CBD) in an agave based syrup with reconstituted terpene profile or the agave-based syrup alone. The emulsification process renders the material virtually odorless allowing for the patient to be blinded.
  • Storage and Stability: store vials at 2-8° C. (36-46° F.).
  • Preparation: emulsified solution.
  • How Supplied: in glass jars with increments and doses labeled on each bottle.
  • Administration: both are to be administered on a q6 to q8 hour basis (e.g., every 6 to 8 hours) by either direct administration or the syrup is to be mixed with 7-up with care being taken to chew the ice. If ineffective, the patient will double the dose. If there is no improvement then the patient will be crossed-over.
  • Adverse Events: THC ingestion has been associated with adverse effects such as agitation; panic disorder; depression and even psychosis and all adverse events will be chronicled based on version 4.
  • Cannabis
  • DESCRIPTION
  • Tetrahydrocannabinol: Cannabidiol (THC:CBD) agave based syrup (15-20 mg THC/10-12 mg CBD) with reconstituted terpene profile versus control agave-based syrup.
  • Cannabis is intended for use as a psychoactive drug or as a medicine. The main psychoactive part of cannabis is tetrahydrocannabinol (THC); it is one of at least 421 known compounds in the plant, including at least 61 other cannabinoids, such as cannabidiol (CBD), cannabinol (CBN), and tetrahydrocannabivarin (THCV).
  • Researchers have subsequently confirmed that THC exerts its most prominent effects via its actions on two types of cannabinoid receptors, the CB1 receptor and the CB2 receptor, both of which are G-protein coupled receptors. The CB1 receptor is found primarily in the brain as well as in some peripheral tissues, and the CB2 receptor is found primarily in peripheral tissues, but is also expressed in neuroglial cells THC appears to alter mood and cognition through its agonist actions on the CB1 receptors, which inhibit a secondary messenger system (adenylate cyclase) in a dose dependent manner. These actions can be blocked by the selective CBlreceptor antagonist SR141716A (rimonabant), which has been shown in clinical trials to be an effective treatment for smoking cessation, weight loss, and as a means of controlling or reducing metabolic syndrome risk factors. However, due to the dysphoric effect of CB1 antagonists, this drug is often discontinued due to these side effects. Via CB1 activation, THC indirectly increases dopamine release and produces psychotropic effects. Cannabidiol also acts as an allosteric modulator of the mu and delta opioid receptors. THC also potentiates the effects of the glycine receptors. The role of these interactions in the “marijuana high” remains elusive.
  • The high lipid-solubility of cannabinoids results in their persisting in the body for long periods of time. Even after a single administration of THC, detectable levels of THC can be found in the body for weeks or longer (depending on the amount administered and the sensitivity of the assessment method). A number of investigators have suggested that this is an important factor in marijuana's effects, perhaps because cannabinoids may accumulate in the body, particularly in the lipid membranes of neurons.
  • In comparison to smoking and inhalation, after oral ingestion, systemic absorption is relatively slow resulting in maximum A9-THC plasma concentration within 1-2 hours which could be delayed by few hours in certain cases. In some subjects, more than one plasma peak was observed. Extensive liver metabolism probably reduces the oral bioavailability of A9-THC by 4-12%. After oral administration, maximum A9-THC plasma concentration was 4.4-11 ng/mL for 20 mg and 2.7-6.3 ng/mL for 15 mg. Much higher concentration of 11-OH THC was produced after ingestion than inhalation. Following assimilation via the blood, A9-THC rapidly penetrates in to fat tissues and highly vascularized tissues including brain and muscle resulting in rapid decrease in plasma concentration. This tissue distribution is followed by slow redistribution of it from the deep fat deposits back into the blood stream. It should be noted that the residual A9-THC levels are maintained in the body for a long time following abuse. The half-life of it for an infrequent user is 1.3 days and for frequent users 5-13 days. After smoking a cigarette containing 16-34 mg of A9-THC, THC—COOH is detectable in plasma for 2-7 days. A clinical study carried out among 52 volunteers showed that THC—COOH was detectable in serum from 3.5 to 74.3 hours. Initial concentration was between 14-49 ng/mL. This was considerably less than the THC—COOH detection time of 25 days in a single chronic user.
  • A9-THC is metabolized in the liver by microsomal hydroxylation and oxidation catalyzed by enzymes of cytochrome P450 (CYP) complex. The average plasma clearance rates have been reported to be 11.8+3 L/hour for women and 14.9+3.7 L/hour for men. Others have determined approximately 36 L/hour for naïve cannabis users and 60 L/hour for regular cannabis users. More than 65% of cannabis is excreted in the feces and approximately 20% is excreted in urine. Most of the cannabis (80-90%) is excreted within 5 days as hydroxylated and carboxylated metabolites. There are eighteen acidic metabolites of cannabis identified in urine and most of these metabolites form a conjugate with glucuronic acid, which increases its water solubility. Among the major metabolites (A9-THC,11-OH-THC, and THCCOOH), THCCOOH is the primary glucuronide conjugate in urine, while 11-OH-THC is the predominant form in feces. Since A9-THC is extremely soluble in lipids, it results in tubular re-absorption, leading to low renal excretion of unchanged drug. Urinary excretion half-life of THCCOOH was observed to be approximately 30 hours after seven days and 44-60 hours after twelve days of monitoring. After smoking approximately 27 mg of A9-THC in a cigarette, 11-OH-THC peak concentration was observed in the urine within two hours in the range of 3.2-53.3 ng/mL, peaking at 77.0+329.7 ng/mL after 3 hours and THCCOOH peaking at 179.4 ng/mL±146.9 after 4 hours.
  • Stability and Storage
  • Store at room temperature in a colored bottle to avoid decomposition of the THC.
  • Preparation
  • The syrup is prepared using CO2 extracted THC which is then decarboxylated. The syrup is composed of agave syrup, glycerin, citric acid, lecithin, THC/CBD oil, coloring and flavoring. Each bottle, marked on the sides in 12 millimeter increments, will contain a total of 150-200 mg of THC and approximately 100-120 mg of CBD and will provide ten doses of medicine. The placebo will be the identical mixture without the addition of THC/CBD oil.
  • Administration
  • The patient will ingest 12 ml of either placebo or medicinal cannabis containing approximately 15-20 mg of THC and 10-12 mg CBD with the plant-specific terpenes reconsituted on a QID basis. The patients will be allowed to double the dose if symptoms to do not resolve.
  • Adverse Events
  • Short-term adverse effects include alterations in short-term memory, sense of time, sensory perception, attention span, problem solving, verbal fluency, reaction time, and psychomotor control. Some users report positive feelings such as mild euphoria and relaxation, while others, particularly naïve users, report anxiety, paranoia, and panic reactions. Depression and anxiety have also been reported as short-term adverse events. The short-term effects of marijuana last approximately 1-4 hours, depending on potency of the marijuana, the route of administration, and the tolerance of the user. Furthermore, there have been reports of adverse cardiac events including arrhythmias associated with a prolonged Q-T interval; hypertension and hypotension; tachycardia; and myocardial infarction. It is much more difficult to assess long-term adverse effects that may be attributable to the consumption of medicinal cannabis. While there is no question that marijuana causes short-term impairments in brain function, the degree to which these impairments are reversible with chronic use is less clear. Some studies have shown that brain function recovers over time, while others demonstrate persistence of subtle, but important, impairments. There is some suggestion that schizophrenia may be associated with long-term usage of cannabis. Lastly, there are the general concerns of smoking associated with cannabis use although that is not of concern as it relates to this study as the cannabis will be ingested and not inhaled.
  • Drug Interactions
  • A 9-THC is metabolized in the liver by microsomal hydroxylation and oxidation catalyzed by enzymes of cytochrome P450 (CYP) complex. As a result any drug that is similarly metabolized may be affected. Particular attention must be given to warfarin or similar products; tadalafil or similar products; and anti-depressants.
  • Treatment Plan and Entry
  • IRB Approval and IRB-Approved Informed Consent
  • Patient Entry and Registration
  • Treatment Plan
  • This is a double-blind phase III prospective randomized two-arm study which will be conducted in patients with chronic pain with a history of at least 3 years use of opiates for analgesia. Patients will be randomized using a computer based randomization program off-site and overseen by the independent observer. Patients will start the study within 2 days of filling their opiate prescription and verification through the Nevada State Prescription Monitoring Program that the patient is receiving narcotics from only a single source. The total morphine milligram equivalents (MME) used weekly by the subject will be calculated based on the CDC conversion table. Subjects will be given a diary to record time and amount of study medication used on a daily basis in addition to recording any adverse events. Diaries will be collected weekly. Patients will be given physician phone number in order to report any adverse event.
  • Week 1. Patients are to use syrup (A or B) as directed on a q 6 hour basis and use their opiates only for breakthrough pain. The patient will be seen at the end of each week and a pill count will be done to determine the quantity of opiate (MME) consumed by the subject and recorded.
  • Weeks 2-7. At the end of week 2 if there has been no improvement as determined by at least a 20% reduction in total MME used compared to the baseline, the patient will crossed over and continued on the new syrup for a minimum of two additional weeks and if no reduction of at least 20% in total MME study treatment will be discontinued. If the patient's consumption of MME decreases by more than 20% within the first two weeks after initial drug assignment or after two weeks after being crossed-over, the patient will continue on the study drug for at least 4 additional weeks. The patient will be followed through the end of the study with collection of all study data.
  • Treatment Modifications
  • Before cross-over has taken place if there is no improvement from the patient's baseline assessment the dose of either the placebo or THC/CBD will be doubled. Within two weeks after cross-over should the total MME used not decrease by at least 20% the subject will be recorded as a failure of study treatment.
  • Study Parameters
  • Observations and Tests
  • The following observations and tests are to be performed and recorded on the
  • Baseline or Day Day Day Day Day Day Days 8, 15, 22,
    PARAMETER Day 1 2 3 4 5 6 7 29, 36, 43
    History & Physical 1
    Medication diary X** X X X X X X 2
    Pill count and MME calculation X** X X X X X X 2
    Gen Chemistry Panel: Electrolytes: 1 3
    CBC c diff: PT/INR
    Toxicity Diary & Assessment X  X X X X X X 2
      • 1. The baseline History and Physical done will be used if performed within 30 days of entry.
      • 2. Patients will return the Medication Diary weekly. The toxicity assessment will be completed daily by the patient and tabulated weekly unless grade 3 or greater toxicity occurs.
      • 3. Additional blood work will be ordered by the treating physician as needed.
  • Evaluation Criteria
  • The MME calculated at study entry, weekly and then at completion will be used to determine treatment course as well as the success or failure of the study drug.
  • The patients will complete a daily medication and toxicity diary and will be assessed weekly.
  • Parameters of Response
  • Amount of opiate consumed by pill count and MME will be recorded in the medication diary and by the physicians conducting the study. The primary outcome is the complete elimination of opiate used to control the subject's symptoms.
  • Secondary outcome is the percentage reduction of opiate used to control the subject's symptoms as measured by pill count and MME.
  • Adverse events will be documented by the study subjects and verified by the physicians conducting the study
  • Duration of Study
  • The duration of the study will be 4 weeks at a minimum unless subject withdraws voluntarily or is caused to withdraw secondary to an adverse event deemed severe enough either by the patient or treating physician to warrant the subject's withdrawal from the protocol prescribed treatment plan.
  • Study Monitoring and Reporting Procedures
  • Adverse Event Reporting For A Commercial Agent
  • Definition of Adverse Events (AE)
  • An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease that occurs in a patient administered a medical treatment, whether the event is considered related or unrelated to the medical treatment. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
  • Definition of Serious Adverse Event (SAE)
  • A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that at any dose:
      • 1. Results in death
      • 2. Is life threatening (i.e., the subject was, in the opinion of the investigator, at immediate risk of death from the event as it occurred); it does not refer to an event which hypothetically might have caused death if it were more severe
      • 3. Requires or prolongs inpatient hospitalization
      • 4. Results in persistent or significant disability/incapacity (i.e., the event causes a substantial disruption of a person's ability to conduct normal life functions)
      • 5. Results in a congenital anomaly/birth defect
      • 6. Requires intervention to prevent permanent impairment or damage
      • 7. Is an important and significant medical event that may not be immediately life threatening or resulting in death or hospitalization but, based upon appropriate medical judgment, may jeopardize the patient/subject or may require intervention to prevent one of the other outcomes listed above.
  • Reporting Expedited Adverse Events
  • An AE report may need to reach multiple destinations. All expedited AEs will be reported to the IRB or the supervising body overseeing this study. Reporting will be modeled after AdEERS submissions. All adverse reactions will be immediately directed to the Study Chair for further action.
  • Note: All deaths on study require both routine and expedited reporting regardless of causality. Attribution to treatment or other cause must be provided.
  • Expedited AE reporting timelines defined:
  • “24 hours; 3 calendar days”—The investigator must initially report the AE within 24 hours of learning of the event followed by a complete report within 3 calendar days of the initial 24-hour report.
  • “7 calendar days”—A complete report on the AE must be submitted within 7 calendar days of the investigator learning of the event. Any medical event equivalent to CTCAE grade 3, 4, or 5 that hospitalization (or prolongation of existing hospitalization) must be reported regardless of attribution and designation as expected or unexpected with the exception ofany events identified as protocol-specific expedited adverse event reporting exclusions.
  • AEs should be reported by the investigator.
  • Pilot Trials Utilizing a Commercial Agent: AdEERS Expedited Reporting Requirements for Adverse Events That Occur Within 30 Days of the Last Dose of Any Study Agent
  • Reporting Requirements for Adverse Events that occur within 30 Days of the Last Dose of the Commercial Agent on Pilot Trials—GUIDELINES TO BE FOLLOWED regarding reporting of AEs to the Principal Investigator and the IRB
  • Grade 3 Grade 3
    Grade 1 Unexpected With Expected
    Unexpected Hospitalization With Hospitalization Grades Grades
    and Grade 2 Grade 2 Without Without 4 & 52 4 & 52
    Expected Unexpected Expected Hospitalization Hospitalization Unexpected Expected
    Unrelated Not Not Not 7 Not 7 Not 7 7
    Unlikely Required Required Required Calendar Required Calendar Required Calendar Calendar
    Days Days Days Days
    Possible Not 7 Not 7 7 7 Not 24-Hrs; 3 7
    Probable Required Calendar Required Calendar Calendar Calendar Required Calendar Calendar
    Definite Days Days Days Days Days Days
    1 Adverse events with attribution of possible, probable, or definite that occur greater than 30 days after the last dose of treatment with a commercial agent require reporting as follows: AdEERS 24-hour notification followed by complete report within 3 calendar days for: Grade 4 and Grade 5unexpected events AdEERS 7 calendar day report:. Grade 3 unexpected events with hospitalization or prolongation of hospitalization and Grade 5 expected events
    2Although an AdEERS 24-hour notification is not required for death clearly related to progressive disease, a full report is required as outlined in the table. Please see exceptions below under the section entitled, “Additional Instructions or Exceptions to AdEERS Expedited Reporting Requirements for Pilot Trials Utilizing a Commercial Agent.” March 2005
  • Any event that results in persistent or significant disabilities/incapacities, congenital anomalies, or birth defects must be reported to the Study Chair if the event occurs following treatment with a commercial agent.
  • Additional Instructions or Exceptions to AdEERS Expedited Reporting Requirements for Pilot Trials Utilizing a Commercial Agent will be applied to this study:
  • In rare cases, pregnancy might occur in clinical trials. Any pregnancy occurring in association with the use of the study medication and the pregnancy outcome must be reported within five days of first awareness.
  • The event of overdose of aprepitant is considered an SAE by the manufacturer. In the event that there is an overdose of aprepitant, report the overdose and any clinical consequences that occur in association with an overdose.
  • Procedures for Expedited Adverse Event Reporting:
  • Expedited Reports: Expedited reports are to be submitted to the study Chair and the IRB using reports similar to the AdEERS.
  • Data Management Forms
  • The following forms must be completed for all patients and must be received in the study office in accordance with the schedule below.
  • Due within
    Form± Weeks Event Copies* Comments
    History and Physical 1 4 Registration 1
    Consent 4 Registratiom 1 Submit to study co-ordinator
    Patient Symptom Diary 4 weekly 1 Submit to study co-ordinator
    Pill count and MME log 2 weekly 1 Submit to study co-ordinator
    T (Toxicity) Form 2 weekly 1 Submit to study co-ordinator
    AE report See protocol 1 Submit to study co-ordinator
    Form R
    2 Registration 1 Submit to study co-ordinator
    1The History and Physical It is not necessary to repeat for this study.
  • Statistical Considerations
  • Study Design
  • This is a randomized, 2-arm, double-blind, placebo-controlled phase III clinical trial evaluating THC/CBD as an aid to stopping opioid patients who are taking opioids due to chronic pain.
  • The overall objective of this study is to evaluate the probability of stopping opioid use within 5 weeks for patients diagnosed with chronic pain and treated with THC/CBD compared to those receiving placebo.
  • Treatment allocation and Emergency Unblinding
  • The subjects enrolled into this study will receive either daily THC/CBD or a placebo. The study treatments will be sequentially allocated from predetermined lists consisting of randomly permuted study treatments within blocks. This allocation procedure will tend to allocate each of the study regimens to nearly an equal number of the enrollees. Other than blocking the treatments, the randomization procedure will not be otherwise constrained to provide an equal number of subjects in each treatment group. The randomized treatment for each individual will remain concealed unless there arises a need for emergency unblinding. Emergency unblinding occurs when the appropriate clinical care of the subject requires knowledge of her study treatment. The study's Principle Investigator will be responsible for reviewing and approving requests for emergency unblinding. An independent statistician will be responsible for revealing the study treatment.
  • Measures of Efficacy and Safety
  • The principal observation for evaluating the therapeutic efficacy and safety of the study regimens are:
  • Primary Endpoints:
  • Primary efficacy endpoint: cessation of opioids for at least 7 days as determined by the treating physician.
  • Primary safety endpoint: Common Terminology Criteria for Adverse Events (CTCAE)—version 4.0.
  • Secondary Endpoints:
  • Weekly morphine equivalency does (MED).
  • Pain Numeric Score (PNS)
  • Enrollment and Target Sample Size
  • The target enrollment for this study is 64 subjects. The estimated accrual rate is 6 subjects per month. At this rate the enrollment period for this study is expected to require at most 1 year.
  • In order to account for the loss in power due to non-compliance, the target sample size will be increased by 2 subjects for each subject who withdraws from the study prior to completing at least 4 weeks of treatment or cannot be adequately evaluated for opioid usage.
  • Study Hypotheses
  • Null Hypotheses for Primary Efficacy Endpoint:
  • Ho: THC/CBD does not increase the probability of stopping opioids within 5 weeks of starting THC/CBD compared to placebo.
  • Type I Error Allocation
  • The type I error for the primary efficacy hypothesis will be 0.025 for a one-tail test.
  • Analytic Procedures for Testing Hypothesis (HO)
  • Primary Analysis:
  • For the primary analysis subjects will be group according to their randomly assigned treatment and they will be included in the analysis, regardless of their compliance with their assigned treatment plan. Individuals who withdraw early from the study without stopping opioids will be classified in the analysis of the primary endpoint as treatment failures (i.e., not stopping opioids).
  • Inferences regarding the clinical significance of THC/CBD will be made based on a Fisher's exact test of the primary study hypothesis.
  • Secondary and Exploratory analyses:
  • A logistic model will be used to assess whether the subject's initial morphine equivalency dose (MED), age or other clinical or demographic factors are treatment effect modifiers.
  • A linear mixed model will be used to model the patients' weekly morphine equivalency dose over time for women randomized to placebo vs those randomized to THC.
  • Statistical Power
  • With 32 subjects treated on each of the study regimens, this design provides 82% chance of rejecting the primary null hypothesis for efficacy when the true probabilities of stopping opioids within 5 weeks are 5% and 35% for placebo and active, respectively.
  • Interim Analyses
  • An interim futility analysis will be performed when there are at least 16 subjects treated and evaluated in each of the randomized treatment groups. If the proportion of the subjects randomly assigned to placebo who stopped all opioid usage within 5 weeks is greater than or equal to the proportion of subjects on THC/CBD, then consideration will be given to stopping the study. Otherwise, the study will continue to accrue until the target enrollment has been attained. If the study is stopped early due to this stopping boundary, then the conclusion of the study will be that it is unlikely that THC/CBD increases the probability of stopping opioid use in patients with chronic pelvic pain
  • If the true probability stopping opioids on THC/CBD is equal to placebo, then there is a 64% chance that this stopping boundary will recommend stopping the study early. On the other hand, if the true probabilities for stopping opioids are 5% and 35% on placebo and THC/CBD, respectively, then this stopping boundary decreases the statistical power of the study by less than 0.5%.
  • Interim and final reports will include an accounting of all subjects registered onto the study, regardless of their eligibility status or compliance to their assigned treatment.
  • The Data Monitoring Committee (DMC) is responsible for reviewing the results of interim analyses. The decision to terminate accrual to the study or to release study results early includes consideration of adverse events, treatment compliance, as well as results from external studies.
  • REFERENCES, EACH OF WHICH IS INCORPORATED BY REFERENCE IN ITS ENTIRETY
      • May M B and Glode A E. Dronabinol for chemotherapy-induced nausea and vomiting unresponsive to anti-emetics. Cancer Manag Res. 2016; 8: 49-55.
      • Maccarrone M, Maldanado R, Casas M, Henze T, and Centonze D. Cannabinoids therapeutic use: what is our current understanding following the introduction of THC, THC:CBD oromucosal spray and others? Expert Review of Clinical Pharmacology. 2017; 10: 443-55.
      • Russo E B. Current Therapeutic Cannabis Controversies and Clinical Trial Design Issues. Front Pharmacol. 2016; 7: 309-339.
      • Lichtman A H, Lux E A, McQuade R, Rossetti s, Sanchez R, Sun W. Wright S, Kornyeyeva E, Fallon M T. Results of a double-blind, randomized, placebo-controlled study of Nabiximols oromucosal spray as an adjunctive therapy in advanced cancer patients with chronic uncontrolled pain.nJ Pain Symptom Manage. 2018; 55: 179-188.
      • Svendsen K B, jensen T S, Bach F W. Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomized doubleblind placebocontrolled crossover trial. BMJmj. 2004: 329; 253.
      • Vermersch P. Sativex® (tetrahydrocannabinol+cannabidiol) and endocannabinoid system modulator: basic features and main clinical data. Expert Rev Neurother. 2011; 114 (Supp): 15-19.
      • Ware M A, Wang T, Shapiro S, Collet Jpand the COMPASS study team. Cannabis for the management of pain: Asessment of safety study (COMPASS). J Pain; 2015 Dec 16 (12): 1233-1242.
      • Perron Be, Bohnert K, Perone A K, Bonn-Miller M O and Ilgen M. Use of prescription pain medications among medical cannabis patients: comparisons of pain levels, functioning, and patterns of alcohol and other drug use. J Stud Alcohol Drugs. 2015; 76(3); 406-13.
      • Lucas P and Walsh Z. Medical cannabis access, use, and substitution for prescription opioids and other substances: A survey of authorized medical cannabis patients. Int J Drug Policy. 2017; 42:30-35.
      • de Vrol ies M, van Rickevorsel D C M, Vissers K C P, Wilder-Smith O H G, van Goor H, Pain and Nociception Neuroscience Research Group. Clin Gastroenterol Hepatol. 2017; 15(7): 1079-1086.
      • Boehnke K F, Litinas E and Clauw D J. Medical cannabis use is associated with decreased opiate medication use in a retrospective cross-sectional survey of patients with chronic pain. J Pain. 2016; 17 (6): 739-44.
      • Mills M. Moguls and Mexicans: The American history of cannabis legalization. The New Econom Mar. 27, 2015. theneweconomy.com.
      • Micholaum R and Shvo Y. Hasish. I. The structure of cannabidiol.Tetrahedron. 1963 Dec; 19(12): 2073-8.
      • Gaoni Y and Micholaum R. Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish.J. Am. Chem. Soc., 1964, 86 (8), pp 1646-1647.
      • Howlett AC1, Barth F, Bonner T I, Cabral G, Casellas P, Devane W A, Felder C C, Herkenham M, Mackie K, Martin B R, Mechoulam R, Pertwee R G. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev. 2002 Jun;54(2):161-202.
      • Breivogel CS1, Childers S R. The functional neuroanatomy of brain cannabinoid receptors. Neurobiol Dis. 1998 December;5(6 Pt B):417-31.
      • Whiting P F, Wolff R E, Deshpande S, Di Niso M, Duffy S, Hemandez A V, Keurentjes J C, Lang S, Misso K, Rider s, Schmidkofer S, Westwood M, Kleijnen J. Cannabinoids for Medical Use: A systematic review and meta-analysis. JAMA. 2015; 313; 2456-2473.
      • Abrams D I, Couey P, Shader S B, Kelly M E, Benowitz N I. Cannabinoid-opioid Interaction in chronic pain. Clin. Pharmacol. Ther. 2011; 90; 844-851.
      • Miller G. Pot and Pain. Hints are emerging that cannabis could be an alternative to opioid painkillers. Science. 2016: 354; 566-568.
      • Gaskin D J. Richard P. Institute of Medicine Committee on Advancing Pain Research, Care, and Education. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education and Research.Washington, DC: The National Academies Press; 2011. Appendix C: The economic costs of pain in the United States; pp. 301-37.
      • Gaskin D J. Richard P. The Economic Costs of Pain in the United States. Journal of Pain. 2012; 13(8):715-24.
      • Whiting P F, Wolff R F, Deshpande S, Di Nisio M, Duffy S, Hemandez A V, Keurenjtes J C, Lang S, Misso K, Ryder S, Schmidkofer S, Westwood M, and Kleijnen J. Cannabinoids for medical use: A systematic review and meta-analysis. JAMA. 2015; 313(24):2456-2473.
      • Rudd R A1, Aleshire N, Zibbell J E, Gladden R M. Increases in Drug and Opioid Overdose Deaths—United States, 2000-2014.MMWR Morb Mortal Wkly Rep. 2016 Jan. 1; 64(50-51):1378-82.
      • Bachhuber M A, Saloner B, Cunningham C O, Barry C L. Medicinal cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010. JAMA Intern. Med. 2014 174; 1668-1673.
      • Mechoulam R. Plant cannabinoids: a neglected pharmacological treasure trive. Br J Pahrmacol. 2005: 146:913-15.
      • Appendino G, Chianese G, Taglialatela-Scafati O. Cannabinoids: occurrence and medicinal chemistry. Curr Med Chem. 2011; 18:1085-1099.
      • Mackie K. Cannabinoid receptors as therapeutic targets. Ann Rev Pharmacol Toxicol. 2006; 46:101-22.
      • Price M R, Baille G L, Thomas A, Stevenson L A, Easson M, Goodwin R, McLean A, McIntosh L, Goodwin G, Walker G, Westwood P, Marrs J, Thomson F, Cowley P, Christopoulos A, Pertwee R G, and Ross R A. Allosteric modulation of the cannabinoid CB1 receptor. Mol Pharmacol. 2005; 68: 1484-1495.
      • Gorzalka B B, Hill M N and Hillard C J. Regulation of endocannabinoid signaling by stress: implications for stress-related affective disorders. Neurisci Biobehav Rev. 2008; 32: 1152-1160.
      • Izzo A A, Borrelli F, Capasso R, et al. Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends Pharmacol Sci. 2009; 30:515-527.
      • Maione S, Costa B, Di Marzo V. Endocannabinoids: a unique opportunity to develop multitarget analgesics. Pain. 2013;154:S87-S93.
      • Costa B, Trovato A E, Comelli F, et al. The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain. Eur J Pharmacol. 2007; 556:75-83.
      • Evans F. Cannabinoids:the separation of central from peripheral effects on a structural basis. Planta Med. 1991;57:S60-S67.
      • Qin N, Neeper M P, Liu Y, et al. TRPV2 is activated by cannabidiol and mediates CGRP release in cultured rat dorsal root ganglion neurons. J Neurosci. 2008; 28:6231-6238
      • Wirth P W, Watson E S, ElSohly M, et al. Anti-inflammatory properties of cannabichromene. Life Sci. 1980; 26:1991-1995.
      • Izzo A A, Capasso R, Aviello G, et al. Inhibitory effect of cannabichromene, a major non-psychotropic cannabinoid extracted from Cannabis sativa, on inflammation-induced hypermotility in mice. Br J Pharmacol. 2012; 166:1444-1460.
      • Maldonado R, Banos J E, Cabanero D. The endocannabinoid system and neuropathic pain. Pain. 2016;157:S23-S32
      • La Porta C, Bura S A, Llorente-Onaindia J, et al. Role of the endocannabinoid system in the emotional manifestations of osteoarthritis pain. Pain. 2015; 156:2001-2012.
      • Paula-Freire L I G, Andersen M L, Molska G R, and Kohn D O. Evaluation of the Antinociceptive Activity of Ocimum gratissimumL. (Lamiaceae) Essential Oil and its isolated Active Principles in Mice. Phytother Res. 2013; 27:1220-1224.
      • Lemberger L, Silberstein S D, Axelrod J and Kopin I J. Marihuana: Studies on the disposition and metabolism of delta-9-tetrahydrocannabinol in man. Science. 2014; 170:1320-22
      • Yamamoto I, Watanabe K Narimatsu S, and Yoshimura H. Recent advances in the metabolism of cannabinoids. Int J Biochem Cell Biol. 1995;27: 741-746.
      • Bellnier T, Brown G W, Ortega T R. Preliminary evaluation of the efficacy, safety, and costs associated with the treatment of chronic pain with medical cannabis. Ment Health Clin [Internet]. 2018; 8(3):110-5.
      • Rong C, Carmona N E, Lee Y L, Ragguett R M, Pan Z, Rosenblat J D, Subramaniapillai M, Shekotikhina M, Almatham F, Alageel A, Mansur R, Ho R C, McIntyre R S. Drug-drug interactions as a result of co-administering A9-THC and CBD with other psychotropic agents. Expert Opin Drug Saf. 2018 January;17(1):51-54.
      • Nicholson A N, Turner C, Stone B M, and Robson P J. Effect of delta-9 tetrahydrocannabinol and cannabidiol on nocturnal sleep and early morning behavior in young adults. J Clin Psychopharmacol. 2004; 24: 305-323.
      • Russo R B. Current therapeutic cannabis controversies and clinical trial design issues. (Review) Frontiers in Pharmacology. 2016; 7: 1-30.
      • Jones R T, Benowitz N, and Bachman J. Clinical studies of cannabis tolerance and dependence. Ann NY Acad Sci. 1976; 282: 221-239.
      • Nutt D, King L A, Saulsbury W, and Blakemore C. Development of a rational scale to assess the harm of drugs of potential misuse. Lancet 2007; 369: 1047-1053.
      • Adams I B, Martin B R. Cannabis: pharmacology and toxicology in animals and humans. Addiction. 1996; 91;1585-614.
      • Grotenhermen F, Russo E. eds.: Cannabis and Cannabinoids: Pharmacology, Toxicology and Therapeutic Potential. Binghampton, N Y: The Haeworth Press, 2002.
      • Sutton I R, Daeninck P: Cannabinoids in the management of intractable chemotherapy-induced nausea and vomiting and cancer-related pain. J Support Oncol. 2006; 4 (10):531-5.
      • Guzman M. Cannabinoids: potential anticancer agents. Nat Rev Cancer. 2003; 3(10):745-55.
      • Sink K, Segovia K, Sink J, et al. Potential anxiogenic effects of cannabinoid CB1 receptor anagonists/inverse agonists in rats: Comparisons between AM4113, AM251, and the benzodiazepine inverse agonist FG-7142. Eur Neuropsychopharm. 2010; 20:112-122.
      • Christensen R, Kristensen P K, Bartels E M et al. Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomized trials. Lancet. 2007; 370: 1706-13.
      • Hudson B D, Hebert T E, M Kelly M E. Ligand and Heterodimer-Directed Signaling of the CB1 Cannabinoid Receptor. Molecular Pharmacology 2010; 77: 1-9.
      • McHugh D, Hu S S J, Rimmerman N et al. N-arachidonoyl glycine, an abundant endogenous lipid, potently drives directed cellular migration trough GPR18, the putative abnormal cannabidiol receptor. Bmc Neuroscience 2010; 11:11-44.
      • Huestis M A. Pharmacokinetics and metabolism of the plant cannabinoids, delta9-tetrahydrocannabinol, cannabidiol and cannabinol. Handb Exp Pharmacol 2005: 657-90.
      • Hollister L E, Gillespie H K, Ohlsson A et al. Do plasma concentrations of delta 9-tetrahydrocannabinol reflect the degree of intoxication? J Clin Pharmacol 198; 21: 171-1775.
      • Lemberger L, Axelrod J, Kopin I J. Metabolism and disposition of delta-9-tetrahydrocannabinol in man. Pharmacol Rev 1971; 23: 371-80.
      • Law B, Mason P A, Moffat A C et al. Forensic aspects of the metabolism and excretion of cannabinoids following oral ingestion of cannabis resin. J Pharm Pharmacol. 1984; 36: 289-94.
      • Karschner E L, Schwilke E W lowe R H et al. Implications of plasma delta-9-tetrahydrocannabinol, 11-hydroxy-THC and 11-nor-9-carboxy-THC concentrations in chronic cannabis smokers. J Anal Toxicol. 2009; 33: 469-77.
      • Owen S M, McBAy A J, Reisner H M, et al. 1251 radioimmunoassay of delta-9-tetrahydrocannabinol in blood and plasma with a solid-phase second-antibody separation method. Clin Chem. 1981; 27: 619-24.
      • Chiarotti M, Costamagna L. Analysis of 11-nor-9-carboxy-delta (9)-tetrahydrocannabinol in biological samples by gas chromatography tandem mass spectrometry (GC/MS-MS). Forensic Scilnt. 2000; 114:1-6.
      • Kogan N M, Mechoulam R. Cannabinoids in health and disease. Dialogues Clin Neurosci. 2007; 9: 413-30.
      • Haggerty G C, Deskin R, Kurtz P J et al. The pharmacological activity of the fatty acid conjugate 11 palmitoyxy-delta 9-tetrahydrocannabinol. Toxicol Appl Pharmacol. 1986; 84: 599-606.
      • Smith-Kielland A, Skuterud B, Morland J. Urinary excretion of 11-nor-9-carboxy-delta 9-tetrahydrocannabinol and cannabinoids in frequent and infrequent drug users. J Anal Toxicol. 1999; 23: 323-332.
      • Huestis M A, Henningfield J E, Cone E J. Blood cannabinoids. I. Absorption of THC and formation of 11-OH-THC and THCCOOH during and after smoking marijuana. J Anal Toxicol. 1992; 16: 276-82.
      • Reiter A, Hake J, Meissner C et al. Time of drug elimination in chronic drug abusers. Case study of 52 patients in a “low-step” detoxification ward. Forensic SciInt. 2001; 119: 248-253.
      • Lowe R H, Abraham T T, Darwin W D et al. Extended urinary Delta9-tetrahydrocannabinol excretion in chronic cannabis users precludes use as a biomarker of new drug exposure. Drug Alcohol Depend. 2009; 105:24-32.
      • Goulle J P, Saussereau E, Lacroix C. Delta-9-tetrahydrocannabinol pharmacokinetics. Ann Pharm Fr. 2008; 66:232-244.
      • Halldin M M, Andersson L K, widman M et al. Further urinary metabolites of deltal-tetrahydrocannabinol in man. Arzneimittelforschung 1982; 32: 1135-1138.
      • Huestis M A, Cone E J. Urinary excretion half-life of 11-nor-9-carboxy-delta-9-tetrahydrocannabinol in humans. Ther Drug Monit. 1998; 20: 570-576.
      • Kelly P, Jones R T. Metabolism of tetrahydrocannabinol in frequent and infrequent marijuana users. J Anal Toxicol. 1992; 16: 228-235.
      • Johanson E K, Hollister L E, Halldin M M. Urinary elimination half-life of delta-1-tetrahydrocannabinol-7-oic acid in heavy marijuana users after smoking. NIDA Res Monogr. 1989; 95: 457-458.
      • Manno J E, Manno B R, Kemp P M et al. Temporal indications of marijuana use can be estimated from plasma and urine concentrations of delta-9-tetrahydrocannabinol, 11-hydroxy-delta9-tetrahydrocannabinol, and 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid. J Anal Toxicol. 2001; 25: 538-549.
      • Iverson L., Cannabis and the brain. Brain. 2003; 126: 1252-70.
      • Hall W. and Degenhardt L. Adverse health effects of non-medical cannabis use. Lancet. 2009; 374: 1383-91.
      • Solowij N, Stephens R S, Roffman R A et al. Cognitive functioning of long-term heavy cannabis users seeking treatment. JAM. 2002; 287: 1123-31. Erratum in JAMA 2002; 287: 1651.
      • National Governors Association Policy Academy Drug Abuse Prevention. “State of Nevada Plan to Reduce Prescription Drug Abuse”. Nevada 2017. (pp 3-56)
      • Centers for Disease Control and Prevention, National Center for Injury and Prevention Control, Division of Unintentional Injury Prevention. Atlanta, Georgia. U.S. Department of Health and Human Services. “Calculating Total Daily Doses of Opioids for Safer Dosage”. www.cdc.gov/drugoverdose/prescribing/guideline.html. Atlanta, Georgia 2017. (pp1-2)
      • National Cancer Institute: Common Terminology Criteria for adverse Events (CTCAE), Version 4.0 Bethesda, Md. U.S. Department of Health and Human Services, National Institutes of Health, 2010.
  • While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims (8)

1-21. (canceled)
22. A method of treating opioid addiction, the method comprising orally administering to a subject in need thereof an effective amount of a liquid pharmaceutical composition in unit dose form to treat the opioid addiction comprising tetrahydrocannabinol (THC) and cannabidiol (CBD) and a terpene; and wherein the liquid pharmaceutical composition comprises 15-20 mg of the THC per dose, and 10-12 mg of the CBD per dose, wherein the subject's opioid use decreases by greater than or equal to 50% within 5 weeks of beginning treatment as determined by morphine equivalency of opioids used.
23. (canceled)
24. The method of claim 22, wherein the liquid pharmaceutical composition is administered every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours.
25. The method of claim 22, wherein the liquid pharmaceutical composition is administered every 6, 8, or 12 hours.
26. (canceled)
27. The method of claim 22, wherein the liquid pharmaceutical composition further comprises a citric acid, a blue agave, a glycerine, a food coloring, or any combination thereof.
28. The method of claim 22, wherein the method further comprises treating a pain.
US18/131,052 2018-02-23 2023-04-05 Cannabis based therapeutic and method of use Active 2039-06-07 US12303488B2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US18/131,052 US12303488B2 (en) 2018-02-23 2023-04-05 Cannabis based therapeutic and method of use
US18/220,856 US12458653B2 (en) 2018-02-23 2023-07-12 Cannabis based therapeutic and method of use

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201862634547P 2018-02-23 2018-02-23
PCT/US2019/019465 WO2019165387A1 (en) 2018-02-23 2019-02-25 Cannabis based therapeutic and method of use
US202016971781A 2020-08-21 2020-08-21
US18/131,052 US12303488B2 (en) 2018-02-23 2023-04-05 Cannabis based therapeutic and method of use

Related Parent Applications (2)

Application Number Title Priority Date Filing Date
PCT/US2019/019465 Continuation WO2019165387A1 (en) 2018-02-23 2019-02-25 Cannabis based therapeutic and method of use
US16/971,781 Continuation US11684604B2 (en) 2018-02-23 2019-02-25 Cannabis based therapeutic and method of use

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US18/220,856 Continuation US12458653B2 (en) 2018-02-23 2023-07-12 Cannabis based therapeutic and method of use

Publications (2)

Publication Number Publication Date
US20230293480A1 true US20230293480A1 (en) 2023-09-21
US12303488B2 US12303488B2 (en) 2025-05-20

Family

ID=65729449

Family Applications (3)

Application Number Title Priority Date Filing Date
US16/971,781 Active 2039-07-13 US11684604B2 (en) 2018-02-23 2019-02-25 Cannabis based therapeutic and method of use
US18/131,052 Active 2039-06-07 US12303488B2 (en) 2018-02-23 2023-04-05 Cannabis based therapeutic and method of use
US18/220,856 Active US12458653B2 (en) 2018-02-23 2023-07-12 Cannabis based therapeutic and method of use

Family Applications Before (1)

Application Number Title Priority Date Filing Date
US16/971,781 Active 2039-07-13 US11684604B2 (en) 2018-02-23 2019-02-25 Cannabis based therapeutic and method of use

Family Applications After (1)

Application Number Title Priority Date Filing Date
US18/220,856 Active US12458653B2 (en) 2018-02-23 2023-07-12 Cannabis based therapeutic and method of use

Country Status (4)

Country Link
US (3) US11684604B2 (en)
EP (2) EP4417252A3 (en)
BR (1) BR112020017023A2 (en)
WO (1) WO2019165387A1 (en)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4417252A3 (en) 2018-02-23 2024-11-06 Yuzu LV LLC Cannabis based therapeutic and method of use
JP2022502471A (en) * 2018-10-10 2022-01-11 ティルレイ,インコーポレイティド Methods and formulations for treating chemotherapy-induced nausea and vomiting
US12409131B2 (en) 2019-10-03 2025-09-09 Pike Therapeutics Usa, Inc. Transdermal delivery of dronabinol
CN114650809A (en) 2019-10-03 2022-06-21 斯塔顿治疗公司 Transdermal delivery of dronabinol
US12016829B2 (en) 2019-10-11 2024-06-25 Pike Therapeutics Inc. Pharmaceutical composition and method for treating seizure disorders
JP7670700B2 (en) 2019-10-11 2025-04-30 パイク セラピューティクス インコーポレイテッド Transdermal pharmaceutical compositions containing cannabidiol (CBD) for the treatment of seizure disorders
US12268699B2 (en) 2019-10-14 2025-04-08 Pike Therapeutics Inc. Transdermal delivery of tetrahydrocannabinol
WO2021074790A1 (en) 2019-10-14 2021-04-22 Pike Therapeutics, Inc., 1219014 B.C. Ltd. Transdermal delivery of cannabidiol
US12121617B2 (en) 2019-10-14 2024-10-22 Pike Therapeutics Inc. Transdermal delivery of cannabidiol
MX2022015799A (en) * 2020-06-12 2023-04-11 Zelira Therapeutics Operations Pty Ltd Composition and method for treating chronic pain.
BR102020023664A2 (en) * 2020-07-02 2022-01-11 Yuzu Llc COMPOSITIONS COMPRISING CANNABIDIOL AND FLAVONONES
CN114149394B (en) * 2020-09-07 2023-06-06 沈阳药科大学 Curcumene derivatives and their preparation and application
CN114149392B (en) * 2020-09-07 2023-06-06 沈阳药科大学 Curcumene Nitrogen-Containing Derivatives and Its Preparation and Application
CN111991406A (en) * 2020-09-25 2020-11-27 吉林农业大学 New use of gastrodin in suppressing opioid addiction
US12029720B2 (en) 2021-04-29 2024-07-09 Tilray Brands, Inc. Cannabidiol-dominant formulations, methods of manufacturing, and uses thereof
US20250158249A1 (en) 2022-02-28 2025-05-15 Panasonic Energy Co., Ltd. Cylindrical non-aqueous electrolyte secondary battery
US12020794B2 (en) * 2022-03-17 2024-06-25 Green Sky Creations LLC Methods and systems for dispensing opioids according to pain-modulating regimen
CN115120583B (en) * 2022-07-08 2023-06-27 浙江中医药大学 Application of phenylpropanoid derivatives in preparation of drugs for preventing and treating liver failure
US20240033274A1 (en) * 2022-07-27 2024-02-01 Stratos IP, Inc. Use of cannabis to mitigate effects of chemical exposure

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017091764A1 (en) * 2015-11-24 2017-06-01 Constance Therapeutics, Inc. Cannabis oil compositions and methods for preparation thereof
WO2017158539A1 (en) * 2016-03-16 2017-09-21 Buzzelet Development And Technologies Ltd Terpene-enriched cannabinoid composition
US11684604B2 (en) * 2018-02-23 2023-06-27 Yuzu Lv Llc Cannabis based therapeutic and method of use

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11793769B2 (en) * 2014-08-25 2023-10-24 Jai Shankar Sukul Device with compositions for delivery to the lungs, the oral mucosa and the brain
JP2017535539A (en) * 2014-10-21 2017-11-30 ユナイテッド カナビス コーポレイション Cannabis extract and its preparation and use
US9375417B2 (en) 2014-12-04 2016-06-28 Mary's Medicinals LLC Transdermal cannabinoid formulations
KR102025680B1 (en) 2015-07-27 2019-09-26 후아웨이 테크놀러지 컴퍼니 리미티드 SDN based ARP implementation method and device
EP3582755A4 (en) 2017-02-15 2020-12-23 Molecular Infusions, LLC FORMULATIONS
US10668044B2 (en) 2017-06-27 2020-06-02 William H. Muscarella Blended cannabis compounds and methods of making the same
CA3071497A1 (en) * 2017-08-13 2019-02-21 Buzzelet Development And Technologies Ltd Terpene-enriched cannabinoid composition and method of treatment
CN110575432B (en) 2018-06-08 2021-10-12 汉义生物科技(北京)有限公司 Composition containing cannabidiol and application of composition in animal products
EP3813786A4 (en) 2018-06-27 2022-06-29 Colabs International Corporation Compositions comprising silicon dioxide-based particles including one or more agents
BR112020027097A2 (en) 2018-07-02 2021-03-30 Companion Sciences Llc COMBINATION COMPOSITIONS OF CANABIDIOL
WO2020021545A1 (en) 2018-07-25 2020-01-30 Bol Pharma Ltd. Cannabidiol and glucosamine for treating inflammatory joint diseases
US11110069B2 (en) 2018-11-02 2021-09-07 Tweed Inc. Composition comprising cannabinoids for relief of pain
WO2020214200A1 (en) 2019-04-19 2020-10-22 Suturegard Medical, Inc. Hemi-bridge and methods of manufacturing and using same

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017091764A1 (en) * 2015-11-24 2017-06-01 Constance Therapeutics, Inc. Cannabis oil compositions and methods for preparation thereof
WO2017158539A1 (en) * 2016-03-16 2017-09-21 Buzzelet Development And Technologies Ltd Terpene-enriched cannabinoid composition
US11684604B2 (en) * 2018-02-23 2023-06-27 Yuzu Lv Llc Cannabis based therapeutic and method of use

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
Dwivedi, Evergreening: A deceptive device in patent rights, Technology in Society 32 (2010) 324–330. *
Feldman, Understanding ‘Evergreening’ : Making Minor Modifications Of Existing Medications To Extend Protections, Health Affairs June 2022 41:6, 801-804 *
Greg Miller, Could pot help solve the U.S. opioid epidemic? Science.org/content/article/could-pot-help-solve-us-opioid-epidemic, Nov 2016, 1-9. *
Hurd, Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage Neurotherapeutics (2015) 12:807–815. *
Reiman, Cannabis as a Substitute for Opioid-Based Pain Medication: Patient Self-Report, Cannabis and Cannabinoid Research 2017, 2.1, 160-166. *
Russo, Frontiers in Pharmacology, September 2016 | Volume 7 | Article 309, 1-19. *

Also Published As

Publication number Publication date
EP3755372A1 (en) 2020-12-30
EP4417252A3 (en) 2024-11-06
BR112020017023A2 (en) 2021-03-02
US20210023044A1 (en) 2021-01-28
US12303488B2 (en) 2025-05-20
WO2019165387A1 (en) 2019-08-29
EP4417252A2 (en) 2024-08-21
US20230346739A1 (en) 2023-11-02
US12458653B2 (en) 2025-11-04
US11684604B2 (en) 2023-06-27

Similar Documents

Publication Publication Date Title
US12303488B2 (en) Cannabis based therapeutic and method of use
Russo Cannabinoids in the management of difficult to treat pain
AU2018100924A4 (en) Composition and method for treating pain
AU2018101357B4 (en) Composition and method for treating autism
US20240293356A1 (en) Cannabinoid Formulations
Robson Abuse potential and psychoactive effects of δ-9-tetrahydrocannabinol and cannabidiol oromucosal spray (Sativex), a new cannabinoid medicine
US20190298683A1 (en) High-strength oral cannabinoid dosage forms
AU2018100928A4 (en) Composition and method for opioid sparing
AU2021215262B2 (en) Composition and method for treating chronic pain
US20210137877A1 (en) Products and methods for using cannabidiol in combination with melatonin to induce sleep
CN110913839A (en) Myrcene and cannabinoid containing compositions targeted to TRPV1
AU2018100925A4 (en) Cannabinoid composition and method for treating PTSD and/or anxiety
Farrimond et al. Non-Δ9tetrahydrocannabinol phytocannabinoids stimulate feeding in rats
AU2021106137A4 (en) Composition and method for treating chronic pain
Adis Medical Writers dtp@ adis. com Individualize treatment when prescribing medical cannabis to older patients as efficacy data remains limited
Krumm DEPARTMENT OF JUSTICE

Legal Events

Date Code Title Description
FEPP Fee payment procedure

Free format text: ENTITY STATUS SET TO UNDISCOUNTED (ORIGINAL EVENT CODE: BIG.); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY

AS Assignment

Owner name: YUZU LV LLC, NEVADA

Free format text: ASSIGNMENT OF ASSIGNOR'S INTEREST;ASSIGNOR:SPIRTOS, NICOLA MICHAEL;REEL/FRAME:063566/0258

Effective date: 20230410

STPP Information on status: patent application and granting procedure in general

Free format text: DOCKETED NEW CASE - READY FOR EXAMINATION

AS Assignment

Owner name: YUZU LV LLC, NEVADA

Free format text: CHANGE OF ADDRESS;ASSIGNOR:YUZU LV LLC;REEL/FRAME:064208/0071

Effective date: 20230627

STPP Information on status: patent application and granting procedure in general

Free format text: NON FINAL ACTION MAILED

STPP Information on status: patent application and granting procedure in general

Free format text: RESPONSE TO NON-FINAL OFFICE ACTION ENTERED AND FORWARDED TO EXAMINER

STCF Information on status: patent grant

Free format text: PATENTED CASE